Cardiology

  • Article | | open

    Calcium signalling downstream of VEGF is essential for VEGF-induced angiogenesis. Here Savage et al. show that Transmembrane Protein 33 (TMEM33) is required for angiogenesis and the endothelial calcium response to VEGF, revealing a function for TMEM33 in multicellular organisms.

    • Aaron M. Savage
    • , Sathishkumar Kurusamy
    • , Yan Chen
    • , Zhen Jiang
    • , Karishma Chhabria
    • , Ryan B. MacDonald
    • , Hyejeong R. Kim
    • , Heather L. Wilson
    • , Fredericus J. M. van Eeden
    • , Angel L. Armesilla
    • , Timothy J. A. Chico
    •  & Robert N. Wilkinson
  • Article | | open

    Nuclear envelopathies are a group of diseases caused by genetic mutations in essential nuclear envelope genes. Here, the authors report a nuclear envelopathy with a homozygous nonsense variant in TOR1AIP1 which leads to changes in the nuclear morphology including large nuclear-spanning channels in patients’ fibroblasts.

    • Boris Fichtman
    • , Fadia Zagairy
    • , Nitzan Biran
    • , Yiftah Barsheshet
    • , Elena Chervinsky
    • , Ziva Ben Neriah
    • , Avraham Shaag
    • , Michael Assa
    • , Orly Elpeleg
    • , Amnon Harel
    •  & Ronen Spiegel
  • Article | | open

    Heart grafts need good vascularization to survive. Here, the authors engineer perfusable constructs of human embryonic stem cell-derived endothelial cells seeded in collagen matrix in patterned microchannels that form anastomosed vessels in vitro and have increased coronary vascular perfusion on transplantation in rats.

    • Meredith A. Redd
    • , Nicole Zeinstra
    • , Wan Qin
    • , Wei Wei
    • , Amy Martinson
    • , Yuliang Wang
    • , Ruikang K. Wang
    • , Charles E. Murry
    •  & Ying Zheng
  • Article | | open

    The establishment of functional vasculatures requires the specification of newly formed vessels into veins and arteries. Here, Neal et al. use a combination of genetic approaches in mice and zebrafish to show that BMP signalling, via ALK3 and SMAD1/5, is required for venous specification during blood vessel development.

    • Alice Neal
    • , Svanhild Nornes
    • , Sophie Payne
    • , Marsha D. Wallace
    • , Martin Fritzsche
    • , Pakavarin Louphrasitthiphol
    • , Robert N. Wilkinson
    • , Kira M. Chouliaras
    • , Ke Liu
    • , Karen Plant
    • , Radhika Sholapurkar
    • , Indrika Ratnayaka
    • , Wiebke Herzog
    • , Gareth Bond
    • , Tim Chico
    • , George Bou-Gharios
    •  & Sarah De Val
  • Article | | open

    In atherosclerotic plaques, transformation of macrophages into foam cells is a key step in initiating the inflammatory response. Here Fan et al. show that casein kinase 2-interacting protein-1 (CKIP-1) limits foam cell formation and atherosclerosis by preventing expression of the scavenger receptor LOX-1 through REGγ-mediated degradation of Oct-1.

    • Jiao Fan
    • , Lifeng Liu
    • , Qingyan Liu
    • , Yu Cui
    • , Binwei Yao
    • , Minghua Zhang
    • , Yabing Gao
    • , Yesheng Fu
    • , Hongmiao Dai
    • , Jingkun Pan
    • , Ya Qiu
    • , Cui Hua Liu
    • , Fuchu He
    • , Yu Wang
    •  & Lingqiang Zhang
  • Article | | open

    GWAS have identified more than 500 genetic loci associated with blood lipid levels. Here, the authors report a genome-wide analysis of interactions between genetic markers and physical activity, and find that physical activity modifies the effects of four genetic loci on HDL or LDL cholesterol.

    • Tuomas O. Kilpeläinen
    • , Amy R. Bentley
    • , Raymond Noordam
    • , Yun Ju Sung
    • , Karen Schwander
    • , Thomas W. Winkler
    • , Hermina Jakupović
    • , Daniel I. Chasman
    • , Alisa Manning
    • , Ioanna Ntalla
    • , Hugues Aschard
    • , Michael R. Brown
    • , Lisa de las Fuentes
    • , Nora Franceschini
    • , Xiuqing Guo
    • , Dina Vojinovic
    • , Stella Aslibekyan
    • , Mary F. Feitosa
    • , Minjung Kho
    • , Solomon K. Musani
    • , Melissa Richard
    • , Heming Wang
    • , Zhe Wang
    • , Traci M. Bartz
    • , Lawrence F. Bielak
    • , Archie Campbell
    • , Rajkumar Dorajoo
    • , Virginia Fisher
    • , Fernando P. Hartwig
    • , Andrea R. V. R. Horimoto
    • , Changwei Li
    • , Kurt K. Lohman
    • , Jonathan Marten
    • , Xueling Sim
    • , Albert V. Smith
    • , Salman M. Tajuddin
    • , Maris Alver
    • , Marzyeh Amini
    • , Mathilde Boissel
    • , Jin Fang Chai
    • , Xu Chen
    • , Jasmin Divers
    • , Evangelos Evangelou
    • , Chuan Gao
    • , Mariaelisa Graff
    • , Sarah E. Harris
    • , Meian He
    • , Fang-Chi Hsu
    • , Anne U. Jackson
    • , Jing Hua Zhao
    • , Aldi T. Kraja
    • , Brigitte Kühnel
    • , Federica Laguzzi
    • , Leo-Pekka Lyytikäinen
    • , Ilja M. Nolte
    • , Rainer Rauramaa
    • , Muhammad Riaz
    • , Antonietta Robino
    • , Rico Rueedi
    • , Heather M. Stringham
    • , Fumihiko Takeuchi
    • , Peter J. van der Most
    • , Tibor V. Varga
    • , Niek Verweij
    • , Erin B. Ware
    • , Wanqing Wen
    • , Xiaoyin Li
    • , Lisa R. Yanek
    • , Najaf Amin
    • , Donna K. Arnett
    • , Eric Boerwinkle
    • , Marco Brumat
    • , Brian Cade
    • , Mickaël Canouil
    • , Yii-Der Ida Chen
    • , Maria Pina Concas
    • , John Connell
    • , Renée de Mutsert
    • , H. Janaka de Silva
    • , Paul S. de Vries
    • , Ayşe Demirkan
    • , Jingzhong Ding
    • , Charles B. Eaton
    • , Jessica D. Faul
    • , Yechiel Friedlander
    • , Kelley P. Gabriel
    • , Mohsen Ghanbari
    • , Franco Giulianini
    • , Chi Charles Gu
    • , Dongfeng Gu
    • , Tamara B. Harris
    • , Jiang He
    • , Sami Heikkinen
    • , Chew-Kiat Heng
    • , Steven C. Hunt
    • , M. Arfan Ikram
    • , Jost B. Jonas
    • , Woon-Puay Koh
    • , Pirjo Komulainen
    • , Jose E. Krieger
    • , Stephen B. Kritchevsky
    • , Zoltán Kutalik
    • , Johanna Kuusisto
    • , Carl D. Langefeld
    • , Claudia Langenberg
    • , Lenore J. Launer
    • , Karin Leander
    • , Rozenn N. Lemaitre
    • , Cora E. Lewis
    • , Jingjing Liang
    • , Behrooz Z. Alizadeh
    • , H. Marike Boezen
    • , Lude Franke
    • , Gerjan Navis
    • , Marianne Rots
    • , Morris Swertz
    • , Bruce H. R. Wolffenbuttel
    • , Cisca Wijmenga
    • , Jianjun Liu
    • , Reedik Mägi
    • , Ani Manichaikul
    • , Thomas Meitinger
    • , Andres Metspalu
    • , Yuri Milaneschi
    • , Karen L. Mohlke
    • , Thomas H. Mosley Jr.
    • , Alison D. Murray
    • , Mike A. Nalls
    • , Ei-Ei Khaing Nang
    • , Christopher P. Nelson
    • , Sotoodehnia Nona
    • , Jill M. Norris
    • , Chiamaka Vivian Nwuba
    • , Jeff O’Connell
    • , Nicholette D. Palmer
    • , George J. Papanicolau
    • , Raha Pazoki
    • , Nancy L. Pedersen
    • , Annette Peters
    • , Patricia A. Peyser
    • , Ozren Polasek
    • , David J. Porteous
    • , Alaitz Poveda
    • , Olli T. Raitakari
    • , Stephen S. Rich
    • , Neil Risch
    • , Jennifer G. Robinson
    • , Lynda M. Rose
    • , Igor Rudan
    • , Pamela J. Schreiner
    • , Robert A. Scott
    • , Stephen S. Sidney
    • , Mario Sims
    • , Jennifer A. Smith
    • , Harold Snieder
    • , Tamar Sofer
    • , John M. Starr
    • , Barbara Sternfeld
    • , Konstantin Strauch
    • , Hua Tang
    • , Kent D. Taylor
    • , Michael Y. Tsai
    • , Jaakko Tuomilehto
    • , André G. Uitterlinden
    • , M. Yldau van der Ende
    • , Diana van Heemst
    • , Trudy Voortman
    • , Melanie Waldenberger
    • , Patrik Wennberg
    • , Gregory Wilson
    • , Yong-Bing Xiang
    • , Jie Yao
    • , Caizheng Yu
    • , Jian-Min Yuan
    • , Wei Zhao
    • , Alan B. Zonderman
    • , Diane M. Becker
    • , Michael Boehnke
    • , Donald W. Bowden
    • , Ulf de Faire
    • , Ian J. Deary
    • , Paul Elliott
    • , Tõnu Esko
    • , Barry I. Freedman
    • , Philippe Froguel
    • , Paolo Gasparini
    • , Christian Gieger
    • , Norihiro Kato
    • , Markku Laakso
    • , Timo A. Lakka
    • , Terho Lehtimäki
    • , Patrik K. E. Magnusson
    • , Albertine J. Oldehinkel
    • , Brenda W. J. H. Penninx
    • , Nilesh J. Samani
    • , Xiao-Ou Shu
    • , Pim van der Harst
    • , Jana V. Van Vliet-Ostaptchouk
    • , Peter Vollenweider
    • , Lynne E. Wagenknecht
    • , Ya X. Wang
    • , Nicholas J. Wareham
    • , David R. Weir
    • , Tangchun Wu
    • , Wei Zheng
    • , Xiaofeng Zhu
    • , Michele K. Evans
    • , Paul W. Franks
    • , Vilmundur Gudnason
    • , Caroline Hayward
    • , Bernardo L. Horta
    • , Tanika N. Kelly
    • , Yongmei Liu
    • , Kari E. North
    • , Alexandre C. Pereira
    • , Paul M. Ridker
    • , E. Shyong Tai
    • , Rob M. van Dam
    • , Ervin R. Fox
    • , Sharon L. R. Kardia
    • , Ching-Ti Liu
    • , Dennis O. Mook-Kanamori
    • , Michael A. Province
    • , Susan Redline
    • , Cornelia M. van Duijn
    • , Jerome I. Rotter
    • , Charles B. Kooperberg
    • , W. James Gauderman
    • , Bruce M. Psaty
    • , Kenneth Rice
    • , Patricia B. Munroe
    • , Myriam Fornage
    • , L. Adrienne Cupples
    • , Charles N. Rotimi
    • , Alanna C. Morrison
    • , Dabeeru C. Rao
    •  & Ruth J. F. Loos
  • Article | | open

    Current treatments for age-related neovascular macular degeneration (nAMD) suffer from limited efficacy. Here, Zhao et al. show that pharmacological inhibition or genetic deletion of the mineralocorticoid receptor (MR) limits choroidal neovascularisation in rodents, and show in a pilot clinical study that targeting the MR pathway may provide clinical benefits in nAMD patiens.

    • Min Zhao
    • , Irmela Mantel
    • , Emmanuelle Gelize
    • , Xinxin Li
    • , Xiaoyue Xie
    • , Alejandro Arboleda
    • , Marie Seminel
    • , Rinath Levy-Boukris
    • , Marilyn Dernigoghossian
    • , Andrea Prunotto
    • , Charlotte Andrieu-Soler
    • , Carlo Rivolta
    • , Jérémie Canonica
    • , Marie-Christine Naud
    • , Sebastian Lechner
    • , Nicolette Farman
    • , Irene Bravo-Osuna
    • , Rocio Herrero-Vanrell
    • , Frederic Jaisser
    •  & Francine Behar-Cohen
  • Article | | open

    Beta II protein kinase C (βIIPKC) activation contributes to heart failure. Here the authors show, in a rat model of myocardial infarction, that heart failure outcome can be improved by selectively inhibiting the interaction between βIIPKC and its downstream mitochondrial target Mitofusin-1, and that this strategy is superior to global βIIPKC inhibition.

    • Julio C. B. Ferreira
    • , Juliane C. Campos
    • , Nir Qvit
    • , Xin Qi
    • , Luiz H. M. Bozi
    • , Luiz R. G. Bechara
    • , Vanessa M. Lima
    • , Bruno B. Queliconi
    • , Marie-Helene Disatnik
    • , Paulo M. M. Dourado
    • , Alicia J. Kowaltowski
    •  & Daria Mochly-Rosen
  • Article | | open

    Imbalanced proteostasis is associated with diverse diseases, including ischemia/reperfusion injury in the heart. Here the authors show that the ATF6 arm of the unfolded protein response can be pharmacologically activated with a small molecule in vivo, providing protection from ischemia/reperfusion injury in the heart, the brain, and the kidney.

    • Erik A. Blackwood
    • , Khalid Azizi
    • , Donna J. Thuerauf
    • , Ryan J. Paxman
    • , Lars Plate
    • , Jeffery W. Kelly
    • , R. Luke Wiseman
    •  & Christopher C. Glembotski
  • Article | | open

    Myocardial tissue undergoes steady functional decline when cultured in vitro. Here, the authors report a protocol for culture of human cardiac slices that allows maintenance of contractility for up to four months, and show that the model is suitable for evaluation of drug safety, as exemplified for drugs interfering with cardiomyocyte repolarization.

    • Carola Fischer
    • , Hendrik Milting
    • , Evelyn Fein
    • , Elisabeth Reiser
    • , Kun Lu
    • , Thomas Seidel
    • , Camilla Schinner
    • , Thomas Schwarzmayr
    • , Rene Schramm
    • , Roland Tomasi
    • , Britta Husse
    • , Xiaochun Cao-Ehlker
    • , Ulrich Pohl
    •  & Andreas Dendorfer
  • Article | | open

    Thrombospondin 4 has been shown to protect the heart and the skeletal muscle by enhancing matrix secretion and membrane stability thanks to its intracellular function. Here the authors show that thrombospondin 3 exacerbates injury-induced cardiomyopathy and promotes destabilization of the cardiomyocyte membrane by impairing integrin trafficking to the sarcolemma.

    • Tobias G. Schips
    • , Davy Vanhoutte
    • , Alexander Vo
    • , Robert N. Correll
    • , Matthew J. Brody
    • , Hadi Khalil
    • , Jason Karch
    • , Andoria Tjondrokoesoemo
    • , Michelle A. Sargent
    • , Marjorie Maillet
    • , Robert S. Ross
    •  & Jeffery D. Molkentin
  • Article | | open

    Gelsolin is an actin severing and capping protein that regulates cytoskeletal remodeling. Here the authors show that gelsolin is negatively regulated in the heart by PI3Kα‐ generated PIP3, and that loss of gelsolin activity prevents adverse cytoskeletal remodeling and heart failure.

    • Vaibhav B. Patel
    • , Pavel Zhabyeyev
    • , Xueyi Chen
    • , Faqi Wang
    • , Manish Paul
    • , Dong Fan
    • , Brent A. McLean
    • , Ratnadeep Basu
    • , Pu Zhang
    • , Saumya Shah
    • , John F. Dawson
    • , W. Glen Pyle
    • , Mousumi Hazra
    • , Zamaneh Kassiri
    • , Saugata Hazra
    • , Bart Vanhaesebroeck
    • , Christopher A. McCulloch
    •  & Gavin Y. Oudit
  • Article | | open

    Studying the genetic underpinnings of physical activity and sleep duration can be confounded by self-reporting. Here, Doherty et al. use data from 91,105 UK Biobank participants, whose activity had been monitored for a week by a wearable device, for genome-wide association analysis and identify 14 loci.

    • Aiden Doherty
    • , Karl Smith-Byrne
    • , Teresa Ferreira
    • , Michael V. Holmes
    • , Chris Holmes
    • , Sara L. Pulit
    •  & Cecilia M. Lindgren
  • Article | | open

    Histone lysine demethylases (KDMs) can mediate transcriptional reprogramming in disease states. Here the authors show that KDM3A promotes left ventricular hypertrophy and cardiac fibrosis by activating the transcription of Timp1, and that pharmacological inhibition of KDM3A attenuates cardiac remodeling induced by pressure overload.

    • Qing-Jun Zhang
    • , Tram Anh T. Tran
    • , Ming Wang
    • , Mark J. Ranek
    • , Kristen M. Kokkonen-Simon
    • , Jason Gao
    • , Xiang Luo
    • , Wei Tan
    • , Viktoriia Kyrychenko
    • , Lan Liao
    • , Jianming Xu
    • , Joseph A. Hill
    • , Eric N. Olson
    • , David A. Kass
    • , Elisabeth D. Martinez
    •  & Zhi-Ping Liu
  • Article | | open

    VEGF-C drives lymphangiogenesis through binding to its receptors VEGFR-2 and VEGFR-3. Here, Durré et al. identify uPARAP/Endo180 as a critical regulator of VEGFR-2/VEGFR-3 heterodimerisation and downstream signaling in response to VEGF-C, and show that uPARAP deletion leads to the formation of hyperbranched vasculatures in pathological conditions.

    • Tania Durré
    • , Florent Morfoisse
    • , Charlotte Erpicum
    • , Marie Ebroin
    • , Silvia Blacher
    • , Melissa García-Caballero
    • , Christophe Deroanne
    • , Thomas Louis
    • , Cédric Balsat
    • , Maureen Van de Velde
    • , Seppo Kaijalainen
    • , Frédéric Kridelka
    • , Lars Engelholm
    • , Ingrid Struman
    • , Kari Alitalo
    • , Niels Behrendt
    • , Jenny Paupert
    •  & Agnès Noel
  • Article | | open

    Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.

    • Nora Franceschini
    • , Claudia Giambartolomei
    • , Paul S. de Vries
    • , Chris Finan
    • , Joshua C. Bis
    • , Rachael P. Huntley
    • , Ruth C. Lovering
    • , Salman M. Tajuddin
    • , Thomas W. Winkler
    • , Misa Graff
    • , Maryam Kavousi
    • , Caroline Dale
    • , Albert V. Smith
    • , Edith Hofer
    • , Elisabeth M. van Leeuwen
    • , Ilja M. Nolte
    • , Lingyi Lu
    • , Markus Scholz
    • , Muralidharan Sargurupremraj
    • , Niina Pitkänen
    • , Oscar Franzén
    • , Peter K. Joshi
    • , Raymond Noordam
    • , Riccardo E. Marioni
    • , Shih-Jen Hwang
    • , Solomon K. Musani
    • , Ulf Schminke
    • , Walter Palmas
    • , Aaron Isaacs
    • , Adolfo Correa
    • , Alan B. Zonderman
    • , Albert Hofman
    • , Alexander Teumer
    • , Amanda J. Cox
    • , André G. Uitterlinden
    • , Andrew Wong
    • , Andries J. Smit
    • , Anne B. Newman
    • , Annie Britton
    • , Arno Ruusalepp
    • , Bengt Sennblad
    • , Bo Hedblad
    • , Bogdan Pasaniuc
    • , Brenda W. Penninx
    • , Carl D. Langefeld
    • , Christina L. Wassel
    • , Christophe Tzourio
    • , Cristiano Fava
    • , Damiano Baldassarre
    • , Daniel H. O’Leary
    • , Daniel Teupser
    • , Diana Kuh
    • , Elena Tremoli
    • , Elmo Mannarino
    • , Enzo Grossi
    • , Eric Boerwinkle
    • , Eric E. Schadt
    • , Erik Ingelsson
    • , Fabrizio Veglia
    • , Fernando Rivadeneira
    • , Frank Beutner
    • , Ganesh Chauhan
    • , Gerardo Heiss
    • , Harold Snieder
    • , Harry Campbell
    • , Henry Völzke
    • , Hugh S. Markus
    • , Ian J. Deary
    • , J. Wouter Jukema
    • , Jacqueline de Graaf
    • , Jacqueline Price
    • , Janne Pott
    • , Jemma C. Hopewell
    • , Jingjing Liang
    • , Joachim Thiery
    • , Jorgen Engmann
    • , Karl Gertow
    • , Kenneth Rice
    • , Kent D. Taylor
    • , Klodian Dhana
    • , Lambertus A. L. M. Kiemeney
    • , Lars Lind
    • , Laura M. Raffield
    • , Lenore J. Launer
    • , Lesca M. Holdt
    • , Marcus Dörr
    • , Martin Dichgans
    • , Matthew Traylor
    • , Matthias Sitzer
    • , Meena Kumari
    • , Mika Kivimaki
    • , Mike A. Nalls
    • , Olle Melander
    • , Olli Raitakari
    • , Oscar H. Franco
    • , Oscar L. Rueda-Ochoa
    • , Panos Roussos
    • , Peter H. Whincup
    • , Philippe Amouyel
    • , Philippe Giral
    • , Pramod Anugu
    • , Quenna Wong
    • , Rainer Malik
    • , Rainer Rauramaa
    • , Ralph Burkhardt
    • , Rebecca Hardy
    • , Reinhold Schmidt
    • , Renée de Mutsert
    • , Richard W. Morris
    • , Rona J. Strawbridge
    • , S. Goya Wannamethee
    • , Sara Hägg
    • , Sonia Shah
    • , Stela McLachlan
    • , Stella Trompet
    • , Sudha Seshadri
    • , Sudhir Kurl
    • , Susan R. Heckbert
    • , Susan Ring
    • , Tamara B. Harris
    • , Terho Lehtimäki
    • , Tessel E. Galesloot
    • , Tina Shah
    • , Ulf de Faire
    • , Vincent Plagnol
    • , Wayne D. Rosamond
    • , Wendy Post
    • , Xiaofeng Zhu
    • , Xiaoling Zhang
    • , Xiuqing Guo
    • , Yasaman Saba
    • , Yukinori Okada
    • , Aniket Mishra
    • , Loes Rutten-Jacobs
    • , Anne-Katrin Giese
    • , Sander W. van der Laan
    • , Solveig Gretarsdottir
    • , Christopher D. Anderson
    • , Michael Chong
    • , Hieab H. H. Adams
    • , Tetsuro Ago
    • , Peter Almgren
    • , Philippe Amouyel
    • , Hakan Ay
    • , Traci M. Bartz
    • , Oscar R. Benavente
    • , Steve Bevan
    • , Giorgio B. Boncoraglio
    • , Robert D. Brown Jr.
    • , Adam S. Butterworth
    • , Caty Carrera
    • , Cara L. Carty
    • , Daniel I. Chasman
    • , Wei-Min Chen
    • , John W. Cole
    • , Ioana Cotlarciuc
    • , Carlos Cruchaga
    • , John Danesh
    • , Paul I. W. de Bakker
    • , Anita L. DeStefano
    • , Marcel den Hoed
    • , Qing Duan
    • , Stefan T. Engelter
    • , Guido J. Falcone
    • , Rebecca F. Gottesman
    • , Raji P. Grewal
    • , Stefan Gustafsson
    • , Jeffrey Haessler
    • , Tamara B. Harris
    • , Ahamad Hassan
    • , Aki S. Havulinna
    • , Elizabeth G. Holliday
    • , George Howard
    • , Fang-Chi Hsu
    • , Hyacinth I. Hyacinth
    • , M. Arfan Ikram
    • , Marguerite R. Irvin
    • , Xueqiu Jian
    • , Jordi Jiménez-Conde
    • , Julie A. Johnson
    • , J. Wouter Jukema
    • , Masahiro Kanai
    • , Keith L. Keene
    • , Brett M. Kissela
    • , Dawn O. Kleindorfer
    • , Charles Kooperberg
    • , Michiaki Kubo
    • , Leslie Lange
    • , Carl D. Langefeld
    • , Claudia Langenberg
    • , Jin-Moo Lee
    • , Robin Lemmens
    • , Didier Leys
    • , Cathryn M. Lewis
    • , Wei-Yu Lin
    • , Arne G. Lindgren
    • , Erik Lorentzen
    • , Patrik K. Magnusson
    • , Jane Maguire
    • , Ani Manichaikul
    • , Patrick F. McArdle
    • , James F. Meschia
    • , Thomas H. Mosley
    • , Toshiharu Ninomiya
    • , Martin J. O’Donnell
    • , Sara L. Pulit
    • , Kristiina Rannikmäe
    • , Alexander P. Reiner
    • , Kathryn M. Rexrode
    • , Stephen S. Rich
    • , Paul M. Ridker
    • , Natalia S. Rost
    • , Peter M. Rothwell
    • , Tatjana Rundek
    • , Ralph L. Sacco
    • , Saori Sakaue
    • , Michele M. Sale
    • , Veikko Salomaa
    • , Bishwa R. Sapkota
    • , Reinhold Schmidt
    • , Carsten O. Schmidt
    • , Ulf Schminke
    • , Pankaj Sharma
    • , Agnieszka Slowik
    • , Cathie L. M. Sudlow
    • , Christian Tanislav
    • , Turgut Tatlisumak
    • , Vincent N. S. Thijs
    • , Gudmar Thorleifsson
    • , Unnur Thorsteinsdottir
    • , Steffen Tiedt
    • , Stella Trompet
    • , Matthew Walters
    • , Nicholas J. Wareham
    • , Sylvia Wassertheil-Smoller
    • , Kerri L. Wiggins
    • , Qiong Yang
    • , Salim Yusuf
    • , Tomi Pastinen
    • , Arno Ruusalepp
    • , Eric E. Schadt
    • , Simon Koplev
    • , Veronica Codoni
    • , Mete Civelek
    • , Nick Smith
    • , David A. Trégouët
    • , Ingrid E. Christophersen
    • , Carolina Roselli
    • , Steven A. Lubitz
    • , Patrick T. Ellinor
    • , E. Shyong Tai
    • , Jaspal S. Kooner
    • , Norihiro Kato
    • , Jiang He
    • , Pim van der Harst
    • , Paul Elliott
    • , John C. Chambers
    • , Fumihiko Takeuchi
    • , Andrew D. Johnson
    • , Dharambir K. Sanghera
    • , Olle Melander
    • , Christina Jern
    • , Daniel Strbian
    • , Israel Fernandez-Cadenas
    • , W. T. Longstreth Jr
    • , Arndt Rolfs
    • , Jun Hata
    • , Daniel Woo
    • , Jonathan Rosand
    • , Guillaume Pare
    • , Danish Saleheen
    • , Kari Stefansson
    • , Bradford B. Worrall
    • , Steven J. Kittner
    • , Joanna M. M. Howson
    • , Yoichiro Kamatani
    • , Abbas Dehghan
    • , Adrie Seldenrijk
    • , Alanna C. Morrison
    • , Anders Hamsten
    • , Bruce M. Psaty
    • , Cornelia M. van Duijn
    • , Deborah A. Lawlor
    • , Dennis O. Mook-Kanamori
    • , Donald W. Bowden
    • , Helena Schmidt
    • , James F. Wilson
    • , James G. Wilson
    • , Jerome I. Rotter
    • , Joanna M. Wardlaw
    • , John Deanfield
    • , Julian Halcox
    • , Leo-Pekka Lyytikäinen
    • , Markus Loeffler
    • , Michele K. Evans
    • , Stéphanie Debette
    • , Steve E. Humphries
    • , Uwe Völker
    • , Vilmundur Gudnason
    • , Aroon D. Hingorani
    • , Johan L. M. Björkegren
    • , Juan P. Casas
    •  & Christopher J. O’Donnell
  • Article | | open

    Accumulated HMG-CoA reductase (HMGCR) limits the cholesterol-lowering effect of statins via a feedback loop. Here the authors developed a compound that degrades HMGCR, thus decreasing cholesterol levels and reducing atherosclerotic plaques.

    • Shi-You Jiang
    • , Hui Li
    • , Jing-Jie Tang
    • , Jie Wang
    • , Jie Luo
    • , Bing Liu
    • , Jin-Kai Wang
    • , Xiong-Jie Shi
    • , Hai-Wei Cui
    • , Jie Tang
    • , Fan Yang
    • , Wei Qi
    • , Wen-Wei Qiu
    •  & Bao-Liang Song
  • Article | | open

    The mechanisms that regulate the activity of Ca2 +/calmodulin-dependent protein kinase II (CaMKII) in the context of heart failure are incompletely understood. Here the authors show that protein arginine methyltransferase 1 (PRMT1) prevents cardiac hyperactivation of CaMKII and heart failure development by methylating CaMKII at arginine residues 9 and 275.

    • Jung-Hoon Pyun
    • , Hyun-Ji Kim
    • , Myong-Ho Jeong
    • , Byeong-Yun Ahn
    • , Tuan Anh Vuong
    • , Dong I. Lee
    • , Seri Choi
    • , Seung-Hoi Koo
    • , Hana Cho
    •  & Jong-Sun Kang
  • Article | | open

    Assessing biological circuit connections in single cells has been intractable due to lack of appropriate tools. Here, Bleck et al. develop a method to assess mitochondrial network connectivity in muscle cells and observe clear differences consistent with differing energy requirements.

    • Christopher K. E. Bleck
    • , Yuho Kim
    • , T. Bradley Willingham
    •  & Brian Glancy
  • Article | | open

    Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, the authors perform discovery GWAS for BP in East Asians and meta-analysis in East Asians and Europeans and report ancestry-specific BP SNPs and selection signals.

    • Fumihiko Takeuchi
    • , Masato Akiyama
    • , Nana Matoba
    • , Tomohiro Katsuya
    • , Masahiro Nakatochi
    • , Yasuharu Tabara
    • , Akira Narita
    • , Woei-Yuh Saw
    • , Sanghoon Moon
    • , Cassandra N. Spracklen
    • , Jin-Fang Chai
    • , Young-Jin Kim
    • , Liang Zhang
    • , Chaolong Wang
    • , Huaixing Li
    • , Honglan Li
    • , Jer-Yuarn Wu
    • , Rajkumar Dorajoo
    • , Jovia L. Nierenberg
    • , Ya Xing Wang
    • , Jing He
    • , Derrick A. Bennett
    • , Atsushi Takahashi
    • , Yukihide Momozawa
    • , Makoto Hirata
    • , Koichi Matsuda
    • , Hiromi Rakugi
    • , Eitaro Nakashima
    • , Masato Isono
    • , Matsuyuki Shirota
    • , Atsushi Hozawa
    • , Sahoko Ichihara
    • , Tatsuaki Matsubara
    • , Ken Yamamoto
    • , Katsuhiko Kohara
    • , Michiya Igase
    • , Sohee Han
    • , Penny Gordon-Larsen
    • , Wei Huang
    • , Nanette R. Lee
    • , Linda S. Adair
    • , Mi Yeong Hwang
    • , Juyoung Lee
    • , Miao Li Chee
    • , Charumathi Sabanayagam
    • , Wanting Zhao
    • , Jianjun Liu
    • , Dermot F. Reilly
    • , Liang Sun
    • , Shaofeng Huo
    • , Todd L. Edwards
    • , Jirong Long
    • , Li-Ching Chang
    • , Chien-Hsiun Chen
    • , Jian-Min Yuan
    • , Woon-Puay Koh
    • , Yechiel Friedlander
    • , Tanika N. Kelly
    • , Wen Bin Wei
    • , Liang Xu
    • , Hui Cai
    • , Yong-Bing Xiang
    • , Kuang Lin
    • , Robert Clarke
    • , Robin G. Walters
    • , Iona Y. Millwood
    • , Liming Li
    • , John C. Chambers
    • , Jaspal S. Kooner
    • , Paul Elliott
    • , Pim van der Harst
    • , Marie Loh
    • , Niek Verweij
    • , Weihua Zhang
    • , Benjamin Lehne
    • , Irene Mateo Leach
    • , Alexander Drong
    • , James Abbott
    • , Sian-Tsung Tan
    • , William R. Scott
    • , Gianluca Campanella
    • , Marc Chadeau-Hyam
    • , Uzma Afzal
    • , Tõnu Esko
    • , Sarah E. Harris
    • , Jaana Hartiala
    • , Marcus E. Kleber
    • , Richa Saxena
    • , Alexandre F. R. Stewart
    • , Tarunveer S. Ahluwalia
    • , Imke Aits
    • , Alexessander Da Silva Couto Alves
    • , Shikta Das
    • , Jemma C. Hopewell
    • , Robert W. Koivula
    • , Leo-Pekka Lyytikäinen
    • , Iris Postmus
    • , Olli T. Raitakari
    • , Robert A. Scott
    • , Rossella Sorice
    • , Vinicius Tragante
    • , Michela Traglia
    • , Jon White
    • , Inês Barroso
    • , Andrew Bjonnes
    • , Rory Collins
    • , Gail Davies
    • , Graciela Delgado
    • , Pieter A. Doevendans
    • , Lude Franke
    • , Ron T. Gansevoort
    • , Tanja B. Grammer
    • , Niels Grarup
    • , Jagvir Grewal
    • , Anna-Liisa Hartikainen
    • , Stanley L. Hazen
    • , Chris Hsu
    • , Lise L. N. Husemoen
    • , Johanne M. Justesen
    • , Meena Kumari
    • , Wolfgang Lieb
    • , David C. M. Liewald
    • , Evelin Mihailov
    • , Lili Milani
    • , Rebecca Mills
    • , Nina Mononen
    • , Kjell Nikus
    • , Teresa Nutile
    • , Sarah Parish
    • , Olov Rolandsson
    • , Daniela Ruggiero
    • , Cinzia F. Sala
    • , Harold Snieder
    • , Thomas H. W. Spasø
    • , Wilko Spiering
    • , John M. Starr
    • , David J. Stott
    • , Daniel O. Stram
    • , Silke Szymczak
    • , W. H. Wilson Tang
    • , Stella Trompet
    • , Väinö Turjanmaa
    • , Marja Vaarasmaki
    • , Wiek H. van Gilst
    • , Dirk J. van Veldhuisen
    • , Jorma S. Viikari
    • , Folkert W. Asselbergs
    • , Marina Ciullo
    • , Andre Franke
    • , Paul W. Franks
    • , Steve Franks
    • , Myron D. Gross
    • , Torben Hansen
    • , Marjo-Riitta Jarvelin
    • , Torben Jørgensen
    • , Wouter J. Jukema
    • , Mika Kähönen
    • , Mika Kivimaki
    • , Terho Lehtimäki
    • , Allan Linneberg
    • , Oluf Pedersen
    • , Nilesh J. Samani
    • , Daniela Toniolo
    • , Hooman Allayee
    • , Ian J. Deary
    • , Winfried März
    • , Andres Metspalu
    • , Cisca Wijmenga
    • , Bruce H. W. Wolffenbuttel
    • , Paolo Vineis
    • , Soterios A. Kyrtopoulos
    • , Jos C. S. Kleinjans
    • , Mark I. McCarthy
    • , James Scott
    • , Zhengming Chen
    • , Makoto Sasaki
    • , Xiao-Ou Shu
    • , Jost B. Jonas
    • , Jiang He
    • , Chew-Kiat Heng
    • , Yuan-Tsong Chen
    • , Wei Zheng
    • , Xu Lin
    • , Yik-Ying Teo
    • , E-Shyong Tai
    • , Ching-Yu Cheng
    • , Tien Yin Wong
    • , Xueling Sim
    • , Karen L. Mohlke
    • , Masayuki Yamamoto
    • , Bong-Jo Kim
    • , Tetsuro Miki
    • , Toru Nabika
    • , Mitsuhiro Yokota
    • , Yoichiro Kamatani
    • , Michiaki Kubo
    •  & Norihiro Kato
  • Article | | open

    Abdominal aortic aneurysms (AAA) are characterized by extensive extracellular matrix degradation. Here Hadi et al. identify a netrin-1/neogenin-based crosstalk between macrophages and vascular smooth muscle cells (VSMCs), leading to the secretion of the matrix metalloproteinase MMP-3 by VSMCs and subsequent matrix degradation in AAA lesions.

    • Tarik Hadi
    • , Ludovic Boytard
    • , Michele Silvestro
    • , Dornazsadat Alebrahim
    • , Samson Jacob
    • , Jordyn Feinstein
    • , Krista Barone
    • , Wes Spiro
    • , Susan Hutchison
    • , Russell Simon
    • , Debra Rateri
    • , Florence Pinet
    • , David Fenyo
    • , Mark Adelman
    • , Kathryn J. Moore
    • , Holger K. Eltzschig
    • , Alan Daugherty
    •  & Bhama Ramkhelawon
  • Article | | open

    Wnt signaling is known to regulate the formation of the blood-brain barrier. Here Hübner et al. dissect the underlying mechanisms using high resolution live imaging in zebrafish, and find that Wnt regulates anastomosis of angiogenic sprouts in the brain by counteracting sphingosine-1-phosphate receptor signaling.

    • Kathleen Hübner
    • , Pauline Cabochette
    • , Rodrigo Diéguez-Hurtado
    • , Cora Wiesner
    • , Yuki Wakayama
    • , Kathrin S. Grassme
    • , Marvin Hubert
    • , Stefan Guenther
    • , Heinz-Georg Belting
    • , Markus Affolter
    • , Ralf H. Adams
    • , Benoit Vanhollebeke
    •  & Wiebke Herzog
  • Article | | open

    Angiogenesis requires dynamic endothelial rearrangements and relative position changes within the vascular tubes. Here the authors show that a PI3K/NUAK1/MYPT1/MLCP pathway regulates actomyosin contractility in endothelial cells and cellular rearrangement during vascular patterning.

    • Ana Angulo-Urarte
    • , Pedro Casado
    • , Sandra D. Castillo
    • , Piotr Kobialka
    • , Maria Paraskevi Kotini
    • , Ana M. Figueiredo
    • , Pau Castel
    • , Vinothini Rajeeve
    • , Maria Milà-Guasch
    • , Jaime Millan
    • , Cora Wiesner
    • , Helena Serra
    • , Laia Muixi
    • , Oriol Casanovas
    • , Francesc Viñals
    • , Markus Affolter
    • , Holger Gerhardt
    • , Stephan Huveneers
    • , Heinz-Georg Belting
    • , Pedro R. Cutillas
    •  & Mariona Graupera
  • Article | | open

    Constitutive deletion of Rcan1 has been previously shown to prevent Angiotensin II-induced aneurysm in mice. Here the authors show that tissue-specific inducible deletion of Rcan1 in vascular cell types predisposes to hypertension-mediated aortic rupture, intramural hematoma, and aneurysm, due to increased GSK-3b-mediated activation of ROCK and induction of a hypercontractile phenotype.

    • Silvia Villahoz
    • , Paula Sofía Yunes-Leites
    • , Nerea Méndez-Barbero
    • , Katia Urso
    • , Elena Bonzon-Kulichenko
    • , Sagrario Ortega
    • , J. Francisco Nistal
    • , Jesus Vazquez
    • , Stefan Offermanns
    • , Juan Miguel Redondo
    •  & Miguel R. Campanero
  • Article | | open

    Rare genetic variants can contribute to complex traits but this contribution is not well understood. Here, the authors analyse deep whole genome sequencing data across 1457 individuals from an isolated Greek population and find association of rare variant burdens with cardiometabolic traits.

    • Arthur Gilly
    • , Daniel Suveges
    • , Karoline Kuchenbaecker
    • , Martin Pollard
    • , Lorraine Southam
    • , Konstantinos Hatzikotoulas
    • , Aliki-Eleni Farmaki
    • , Thea Bjornland
    • , Ryan Waples
    • , Emil V. R. Appel
    • , Elisabetta Casalone
    • , Giorgio Melloni
    • , Britt Kilian
    • , Nigel W. Rayner
    • , Ioanna Ntalla
    • , Kousik Kundu
    • , Klaudia Walter
    • , John Danesh
    • , Adam Butterworth
    • , Inês Barroso
    • , Emmanouil Tsafantakis
    • , George Dedoussis
    • , Ida Moltke
    •  & Eleftheria Zeggini
  • Article | | open

    Increased glycolysis and inflammatory responses have been observed in endothelial cells exposed to disturbed flow. However, the role of endothelial glycolysis in atherosclerosis is unclear. Here the authors unveil a protective role for glycolysis by showing that endothelial deletion of Prkaa1 accelerates atherosclerosis in hyperlipidemic mice through a reduction of glycolytic metabolism.

    • Qiuhua Yang
    • , Jiean Xu
    • , Qian Ma
    • , Zhiping Liu
    • , Varadarajan Sudhahar
    • , Yapeng Cao
    • , Lina Wang
    • , Xianqiu Zeng
    • , Yaqi Zhou
    • , Min Zhang
    • , Yiming Xu
    • , Yong Wang
    • , Neal L. Weintraub
    • , Chunxiang Zhang
    • , Tohru Fukai
    • , Chaodong Wu
    • , Lei Huang
    • , Zhen Han
    • , Tao Wang
    • , David J. Fulton
    • , Mei Hong
    •  & Yuqing Huo
  • Article | | open

    Optogenetic tools enable precise experimental control of the behaviour of cells. Here, the authors introduce a genetically-encoded two-protein system that enables silencing of excitable cells such as neurons and cardiomyocytes using blue light, and demonstrate its utility both in vitro and In vivo.

    • Yinth Andrea Bernal Sierra
    • , Benjamin R. Rost
    • , Martin Pofahl
    • , António Miguel Fernandes
    • , Ramona A. Kopton
    • , Sylvain Moser
    • , Dominik Holtkamp
    • , Nicola Masala
    • , Prateep Beed
    • , John J. Tukker
    • , Silvia Oldani
    • , Wolfgang Bönigk
    • , Peter Kohl
    • , Herwig Baier
    • , Franziska Schneider-Warme
    • , Peter Hegemann
    • , Heinz Beck
    • , Reinhard Seifert
    •  & Dietmar Schmitz
  • Article | | open

    A small percentage of cardiomyocytes (CM) are of neural crest origin but the function of such cells in the adult zebrafish is unclear. Here, the authors identify this CM subpopulation as expressing the Notch ligand jag2b and if deleted in the embryo, cause severe hypertrophic cardiomyopathy in adulthood.

    • Sarah Abdul-Wajid
    • , Bradley L. Demarest
    •  & H. Joseph Yost
  • Article | | open

    Vascular smooth muscle cell (VSMC) accumulation is associated with cardiovascular disease. Here, the authors combine single-cell RNA sequencing with lineage labelling to profile VSMC heterogeneity in healthy mice. They show that upregulation of Sca1 in a rare VSMC subpopulation marks a cell phenotype that is prevalent in disease.

    • Lina Dobnikar
    • , Annabel L. Taylor
    • , Joel Chappell
    • , Phoebe Oldach
    • , Jennifer L. Harman
    • , Erin Oerton
    • , Elaine Dzierzak
    • , Martin R. Bennett
    • , Mikhail Spivakov
    •  & Helle F. Jørgensen
  • Article | | open

    The mechanisms underlying the transition from cardiac hypertrophy to heart failure following pressure overload are incompletely understood. Here the authors identify the gene programs encoding the morphological and functional characteristics of cardiomyocytes during the transition from early hypertrophy to heart failure via single-cell transcriptomics, establishing a key role for p53 signalling.

    • Seitaro Nomura
    • , Masahiro Satoh
    • , Takanori Fujita
    • , Tomoaki Higo
    • , Tomokazu Sumida
    • , Toshiyuki Ko
    • , Toshihiro Yamaguchi
    • , Takashige Tobita
    • , Atsuhiko T. Naito
    • , Masamichi Ito
    • , Kanna Fujita
    • , Mutsuo Harada
    • , Haruhiro Toko
    • , Yoshio Kobayashi
    • , Kaoru Ito
    • , Eiki Takimoto
    • , Hiroshi Akazawa
    • , Hiroyuki Morita
    • , Hiroyuki Aburatani
    •  & Issei Komuro
  • Article | | open

    The cardiac autonomic nervous system produces various neuropeptides, such as neurokinin substance-P (Sub-P), whose function remains largely unclear. Here, authors show that Sub-P causes a receptor-mediated prolongation of the atrial action potential through a reduced background potassium current, and prevents atrial fibrillation.

    • Marieke W. Veldkamp
    • , Guillaume S. C. Geuzebroek
    • , Antonius Baartscheer
    • , Arie O. Verkerk
    • , Cees A. Schumacher
    • , Gedeon G. Suarez
    • , Wouter R. Berger
    • , Simona Casini
    • , Shirley C. M. van Amersfoorth
    • , Koen T. Scholman
    • , Antoine H. G. Driessen
    • , Charly N. W. Belterman
    • , Antoni C. G. van Ginneken
    • , Joris R. de Groot
    • , Jacques M. T. de Bakker
    • , Carol Ann Remme
    • , Bas J. Boukens
    •  & Ruben Coronel
  • Article | | open

    Ischemic reperfusion or nutrient deprivation that produces reactive oxygen species can lead to a loss of muscle contractile function. Here the authors show that glutathionylation of the lysine methyltransferase SMYD2 contributes to degradation or disassembly of sarcomeres.

    • Dhanushka N. P. Munkanatta Godage
    • , Garrett C. VanHecke
    • , Kusal T. G. Samarasinghe
    • , Han-Zhong Feng
    • , Mark Hiske
    • , Joshua Holcomb
    • , Zhe Yang
    • , Jian-Ping Jin
    • , Charles S. Chung
    •  & Young-Hoon Ahn
  • Article | | open

    Common genetic variants in structural proteins contribute to risk of atrial fibrillation (AF). Here, using whole-exome sequencing, the authors identify rare truncating variants in TTN that associate with familial and early-onset AF and show defects in cardiac sarcomere assembly in ttn.2-mutant zebrafish.

    • Gustav Ahlberg
    • , Lena Refsgaard
    • , Pia R. Lundegaard
    • , Laura Andreasen
    • , Mattis F. Ranthe
    • , Nora Linscheid
    • , Jonas B. Nielsen
    • , Mads Melbye
    • , Stig Haunsø
    • , Ahmad Sajadieh
    • , Lu Camp
    • , Søren-Peter Olesen
    • , Simon Rasmussen
    • , Alicia Lundby
    • , Patrick T. Ellinor
    • , Anders G. Holst
    • , Jesper H. Svendsen
    •  & Morten S. Olesen
  • Article | | open

    Nitric oxide (NO) inhibits thrombosis in part by stimulating cyclic guanosine monophosphate (cGMP) production and cGMP-dependent protein kinase I (cGKI) activity in platelets. Here, Wen et al. develop a cGMP sensor mouse to follow cGMP dynamics in platelets, and find that shear stress activates NO-cGMP-cGKI signaling during platelet aggregation to limit thrombosis.

    • Lai Wen
    • , Susanne Feil
    • , Markus Wolters
    • , Martin Thunemann
    • , Frank Regler
    • , Kjestine Schmidt
    • , Andreas Friebe
    • , Marcus Olbrich
    • , Harald Langer
    • , Meinrad Gawaz
    • , Cor de Wit
    •  & Robert Feil
  • Article | | open

    Genetic variants in ACTB and ACTG1 have been associated with Baraitser-Winter Cerebrofrontofacial syndrome. Here, the authors report of a syndromic thrombocytopenia caused by variants in ACTB exons 5 or 6 that compromise the organization and coupling of the cytoskeleton, leading to impaired platelet maturation.

    • Sharissa L. Latham
    • , Nadja Ehmke
    • , Patrick Y. A. Reinke
    • , Manuel H. Taft
    • , Dorothee Eicke
    • , Theresia Reindl
    • , Werner Stenzel
    • , Michael J. Lyons
    • , Michael J. Friez
    • , Jennifer A. Lee
    • , Ramona Hecker
    • , Michael C. Frühwald
    • , Kerstin Becker
    • , Teresa M. Neuhann
    • , Denise Horn
    • , Evelin Schrock
    • , Indra Niehaus
    • , Katharina Sarnow
    • , Konrad Grützmann
    • , Luzie Gawehn
    • , Barbara Klink
    • , Andreas Rump
    • , Christine Chaponnier
    • , Constanca Figueiredo
    • , Ralf Knöfler
    • , Dietmar J. Manstein
    •  & Nataliya Di Donato
  • Article | | open

    Due to the limited proliferation capacity of adult mammalian cardiomyocytes, the human heart has negligible regenerative capacity after injury. Here the authors show that a Hedgehog-Gli1-Mycn signaling cascade regulates cardiomyocyte proliferation and cardiac regeneration from amphibians to mammals.

    • Bhairab N. Singh
    • , Naoko Koyano-Nakagawa
    • , Wuming Gong
    • , Ivan P. Moskowitz
    • , Cyprian V. Weaver
    • , Elizabeth Braunlin
    • , Satyabrata Das
    • , Jop H. van Berlo
    • , Mary G. Garry
    •  & Daniel J. Garry
  • Article | | open

    The glycolytic enzyme pyruvate kinase M2 (PKM2) is required for nucleotide synthesis and cell proliferation. Using gene expression and metabolomics analyses, the authors here show that PKM2 regulates methionine metabolism and DNA methylation in endothelial cells.

    • Oliver A. Stone
    • , Mohamed El-Brolosy
    • , Kerstin Wilhelm
    • , Xiaojing Liu
    • , Ana M. Romão
    • , Elisabetta Grillo
    • , Jason K. H. Lai
    • , Stefan Günther
    • , Sylvia Jeratsch
    • , Carsten Kuenne
    • , I-Ching Lee
    • , Thomas Braun
    • , Massimo M. Santoro
    • , Jason W. Locasale
    • , Michael Potente
    •  & Didier Y. R. Stainier
  • Article | | open

    Long noncoding RNAs have been shown to play a role in cardiovascular disease. Here, the authors identify a lncRNA named CCRR, whose downregulation in failing hearts causes cardiac conduction disturbances by altering the endocytic trafficking of Cx43.

    • Yong Zhang
    • , Lihua Sun
    • , Lina Xuan
    • , Zhenwei Pan
    • , Xueling Hu
    • , Hongyu Liu
    • , Yunlong Bai
    • , Lei Jiao
    • , Zhange Li
    • , Lina Cui
    • , Xiaoxue Wang
    • , Siqi Wang
    • , Tingting Yu
    • , Bingbing Feng
    • , Ying Guo
    • , Zonghong Liu
    • , Weixin Meng
    • , Hequn Ren
    • , Jiyuan Zhu
    • , Xuyun Zhao
    • , Chao Yang
    • , Ying Zhang
    • , Chaoqian Xu
    • , Zhiguo Wang
    • , Yanjie Lu
    • , Hongli Shan
    •  & Baofeng Yang
  • Article | | open

    Mitochondrial protein synthesis requires charging a mitochondrial tRNA with its amino acid. Here, the authors describe pathogenic variants in the GatCAB protein complex genes required for the generation of glutaminyl-mt-tRNAGln, that impairs mitochondrial translation and presents with cardiomyopathy.

    • Marisa W. Friederich
    • , Sharita Timal
    • , Christopher A. Powell
    • , Cristina Dallabona
    • , Alina Kurolap
    • , Sara Palacios-Zambrano
    • , Drago Bratkovic
    • , Terry G. J. Derks
    • , David Bick
    • , Katelijne Bouman
    • , Kathryn C. Chatfield
    • , Nadine Damouny-Naoum
    • , Megan K. Dishop
    • , Tzipora C. Falik-Zaccai
    • , Fuad Fares
    • , Ayalla Fedida
    • , Ileana Ferrero
    • , Renata C. Gallagher
    • , Rafael Garesse
    • , Micol Gilberti
    • , Cristina González
    • , Katherine Gowan
    • , Clair Habib
    • , Rebecca K. Halligan
    • , Limor Kalfon
    • , Kaz Knight
    • , Dirk Lefeber
    • , Laura Mamblona
    • , Hanna Mandel
    • , Adi Mory
    • , John Ottoson
    • , Tamar Paperna
    • , Ger J. M. Pruijn
    • , Pedro F. Rebelo-Guiomar
    • , Ann Saada
    • , Bruno Sainz Jr.
    • , Hayley Salvemini
    • , Mirthe H. Schoots
    • , Jan A. Smeitink
    • , Maciej J. Szukszto
    • , Hendrik J. ter Horst
    • , Frans van den Brandt
    • , Francjan J. van Spronsen
    • , Joris A. Veltman
    • , Eric Wartchow
    • , Liesbeth T. Wintjes
    • , Yaniv Zohar
    • , Miguel A. Fernández-Moreno
    • , Hagit N. Baris
    • , Claudia Donnini
    • , Michal Minczuk
    • , Richard J. Rodenburg
    •  & Johan L. K. Van Hove
  • Article | | open

    Excessive production of reactive oxygen species (ROS) is associated with cardiac dysfunction, but the causal role of ROS remains poorly understood. Here the authors use an in vivo chemogenetic approach to develop a heart failure model in which generation of hydrogen peroxide in the heart leads to systolic heart failure without fibrotic remodeling.

    • Benjamin Steinhorn
    • , Andrea Sorrentino
    • , Sachin Badole
    • , Yulia Bogdanova
    • , Vsevolod Belousov
    •  & Thomas Michel
  • Article | | open

    Hypertrophic cardiomyopathy (HCM) is caused by point mutations in sarcomeric proteins. Here the authors develop an optimized model of the sequestered state of cardiac myosin and define the features affecting the lever arm compliance, allowing them to group mutations in classes and to elucidate the molecular mechanisms leading to cardiac dysfunction in HCM.

    • Julien Robert-Paganin
    • , Daniel Auguin
    •  & Anne Houdusse
  • Article | | open

    Mutations in the voltage-gated K+ channel human ether-a-go-go-related gene (hERG) lead to Long-QT syndrome, causing life-threatening cardiac arrhythmia. Here the authors use C. elegans as a platform to run a channelopathy drug screen, identifying drugs to target hERG mutants.

    • Qiang Jiang
    • , Kai Li
    • , Wen-Jing Lu
    • , Shuang Li
    • , Xin Chen
    • , Xi-Juan Liu
    • , Jie Yuan
    • , Qiurong Ding
    • , Feng Lan
    •  & Shi-Qing Cai
  • Article | | open

    Metabolic reprogramming of smooth muscle cells (SMCs) plays an important role in the pathogenesis of pulmonary arterial hypertension (PAH). Here, Dai et al. show that the glycolytic enzyme alpha-enolase contributes to this reprogramming, and that its inhibition limits SMC proliferation and disease progression in animal models of PAH.

    • Jingbo Dai
    • , Qiyuan Zhou
    • , Jiwang Chen
    • , Megan L. Rexius-Hall
    • , Jalees Rehman
    •  & Guofei Zhou
  • Article | | open

    Omecamtiv mecarbil (OM) is a positive cardiac inotrope in clinical trials for the treatment of heart failure whose mechanism of action is incompletely understood. Here the authors show that OM inhibits myosin's working stroke and prolongs actomyosin attachment and propose a model that reconciles the OM-induced increase in cardiac performance in vivo with the inhibitory actions observed in vitro.

    • Michael S. Woody
    • , Michael J. Greenberg
    • , Bipasha Barua
    • , Donald A. Winkelmann
    • , Yale E. Goldman
    •  & E. Michael Ostap
  • Article | | open

    The processes regulating cardiomyocyte (CM) maturation are unclear. Here, the authors show that serum response factor regulates CM maturation only in neonatal CMs through stage-specific chromatin occupancy that affects cell size, sarcomere and transverse-tubule organization, and mitochondria

    • Yuxuan Guo
    • , Blake D. Jardin
    • , Pingzhu Zhou
    • , Isha Sethi
    • , Brynn N. Akerberg
    • , Christopher N Toepfer
    • , Yulan Ai
    • , Yifei Li
    • , Qing Ma
    • , Silvia Guatimosim
    • , Yongwu Hu
    • , Grigor Varuzhanyan
    • , Nathan J. VanDusen
    • , Donghui Zhang
    • , David C. Chan
    • , Guo-Cheng Yuan
    • , Christine E. Seidman
    • , Jonathan G. Seidman
    •  & William T. Pu
  • Article | | open

    Activation of integrin αIIbβ3 at the surface of platelets is required for their aggregation and for thrombus formation. Here Xu et al. identify apolipoprotein A-IV as a novel ligand for platelet αIIbβ3 integrin, and find it inhibits platelet aggregation and thrombosis.

    • Xiaohong Ruby Xu
    • , Yiming Wang
    • , Reheman Adili
    • , Lining Ju
    • , Christopher M. Spring
    • , Joseph Wuxun Jin
    • , Hong Yang
    • , Miguel A. D. Neves
    • , Pingguo Chen
    • , Yan Yang
    • , Xi Lei
    • , Yunfeng Chen
    • , Reid C. Gallant
    • , Miao Xu
    • , Hailong Zhang
    • , Jina Song
    • , Peifeng Ke
    • , Dan Zhang
    • , Naadiya Carrim
    • , Si-Yang Yu
    • , Guangheng Zhu
    • , Yi-Min She
    • , Terry Cyr
    • , Wenbin Fu
    • , Guoqing Liu
    • , Philip W. Connelly
    • , Margaret L. Rand
    • , Khosrow Adeli
    • , John Freedman
    • , Jeffrey E. Lee
    • , Patrick Tso
    • , Patrizia Marchese
    • , W. Sean Davidson
    • , Shaun P. Jackson
    • , Cheng Zhu
    • , Zaverio M. Ruggeri
    •  & Heyu Ni
  • Article | | open

    During the formation of the zebrafish dorsal longitudinal anastomotic vessel, blood vessels connect in a process called anastomosis. Using live imaging, the authors here show that endothelial cell movements during blood vessel anastomosis are associated with oscillating lamellipodia-like structures, oriented in the direction of the movements and emerging at endothelial cell junctions.

    • Ilkka Paatero
    • , Loïc Sauteur
    • , Minkyoung Lee
    • , Anne K. Lagendijk
    • , Daniel Heutschi
    • , Cora Wiesner
    • , Camilo Guzmán
    • , Dimitri Bieli
    • , Benjamin M. Hogan
    • , Markus Affolter
    •  & Heinz-Georg Belting
  • Article | | open

    Pericytes are perivascular cells that regulate blood vessel formation and function. Here Dubrac et al. show that pericyte recruitment contributes to pathological neovascularisation in a mouse model of ischemic retinopathy, and that this depends on the regulation of PDGF-B signaling by NCK adaptor proteins.

    • Alexandre Dubrac
    • , Steffen E. Künzel
    • , Sandrine H. Künzel
    • , Jinyu Li
    • , Rachana Radhamani Chandran
    • , Kathleen Martin
    • , Daniel M. Greif
    • , Ralf H. Adams
    •  & Anne Eichmann
  • Article | | open

    The molecular mechanisms leading to heart failure in patients with Duchenne muscular dystrophy are unclear. Here the authors show that NF-κB is activated in the heart of dystrophin-deficient mice and that its ablation rescues cardiac function through chromatin remodeling and activation of gene expression.

    • Jennifer M. Peterson
    • , David J. Wang
    • , Vikram Shettigar
    • , Steve R. Roof
    • , Benjamin D. Canan
    • , Nadine Bakkar
    • , Jonathan Shintaku
    • , Jin-Mo Gu
    • , Sean C. Little
    • , Nivedita M. Ratnam
    • , Priya Londhe
    • , Leina Lu
    • , Christopher E. Gaw
    • , Jennifer M. Petrosino
    • , Sandya Liyanarachchi
    • , Huating Wang
    • , Paul M. L. Janssen
    • , Jonathan P. Davis
    • , Mark T. Ziolo
    • , Sudarshana M. Sharma
    •  & Denis C. Guttridge