Cardiology

  • Article
    | Open Access

    The kidney is vascularized with highly specialized and zonated endothelial cells that are essential for its filtration function. Here, Barry et al. provide a single-cell RNA sequencing analysis of the kidney vasculature that highlights its transcriptional heterogeneity and uncovers pathways important for its development and function.

    • David M. Barry
    • , Elizabeth A. McMillan
    • , Balvir Kunar
    • , Raphael Lis
    • , Tuo Zhang
    • , Tyler Lu
    • , Edward Daniel
    • , Masataka Yokoyama
    • , Jesus M. Gomez-Salinero
    • , Angara Sureshbabu
    • , Ondine Cleaver
    • , Annarita Di Lorenzo
    • , Mary E. Choi
    • , Jenny Xiang
    • , David Redmond
    • , Sina Y. Rabbany
    • , Thangamani Muthukumar
    •  & Shahin Rafii
  • Article
    | Open Access

    Integrin-linked kinase (ILK) is an important mediator of integrin signaling. Here Park et al. show that mice with endothelial-specific deletion of Ilk develop vascular defects that resemble familial exudative vitreoretinopathy, and identify mutations in ILK in patients with exudative vitreoretinopathy suggesting a potential role in human pathogenesis.

    • Hongryeol Park
    • , Hiroyuki Yamamoto
    • , Lucas Mohn
    • , Lea Ambühl
    • , Kenichi Kanai
    • , Inga Schmidt
    • , Kee-Pyo Kim
    • , Alessia Fraccaroli
    • , Silke Feil
    • , Harald J. Junge
    • , Eloi Montanez
    • , Wolfgang Berger
    •  & Ralf H. Adams
  • Article
    | Open Access

    Pulmonary arterial hypertension (PAH) is characterised by progressive pulmonary vascular remodelling. Here, Arnold et al. develop a therapeutic antibody targeting osteoprotegerin and find it attenuates pulmonary vascular remodelling in multiple rodent models of PAH, alone or in combination with standard of care vasodilator therapy.

    • Nadine D. Arnold
    • , Josephine A. Pickworth
    • , Laura E. West
    • , Sarah Dawson
    • , Joana A. Carvalho
    • , Helen Casbolt
    • , Adam T. Braithwaite
    • , James Iremonger
    • , Lewis Renshall
    • , Volker Germaschewski
    • , Matthew McCourt
    • , Philip Bland-Ward
    • , Hager Kowash
    • , Abdul G. Hameed
    • , Alexander M. K. Rothman
    • , Maria G. Frid
    • , A. A. Roger Thompson
    • , Holly R. Evans
    • , Mark Southwood
    • , Nicholas W. Morrell
    • , David C. Crossman
    • , Moira K. B. Whyte
    • , Kurt R. Stenmark
    • , Christopher M. Newman
    • , David G. Kiely
    • , Sheila E. Francis
    •  & Allan Lawrie
  • Article
    | Open Access

    The risk of fatal stroke is increased in children, adolescent, and young (<40 years) cancer patients after diagnosis. Here, the authors report a retrospective, population-based study and show that the risk of stroke among cancer patients is twice that of the general population and rises with longer follow up time.

    • Nicholas G. Zaorsky
    • , Ying Zhang
    • , Leila T. Tchelebi
    • , Heath B. Mackley
    • , Vernon M. Chinchilli
    •  & Brad E. Zacharia
  • Article
    | Open Access

    Sleep duration is associated with an adverse lipid profile. Here, the authors perform genome-wide gene-by-sleep interaction analysis and find 49 previously unreported lipid loci when considering short or long total sleep time.

    • Raymond Noordam
    • , Maxime M. Bos
    • , Heming Wang
    • , Thomas W. Winkler
    • , Amy R. Bentley
    • , Tuomas O. Kilpeläinen
    • , Paul S. de Vries
    • , Yun Ju Sung
    • , Karen Schwander
    • , Brian E. Cade
    • , Alisa Manning
    • , Hugues Aschard
    • , Michael R. Brown
    • , Han Chen
    • , Nora Franceschini
    • , Solomon K. Musani
    • , Melissa Richard
    • , Dina Vojinovic
    • , Stella Aslibekyan
    • , Traci M. Bartz
    • , Lisa de las Fuentes
    • , Mary Feitosa
    • , Andrea R. Horimoto
    • , Marjan Ilkov
    • , Minjung Kho
    • , Aldi Kraja
    • , Changwei Li
    • , Elise Lim
    • , Yongmei Liu
    • , Dennis O. Mook-Kanamori
    • , Tuomo Rankinen
    • , Salman M. Tajuddin
    • , Ashley van der Spek
    • , Zhe Wang
    • , Jonathan Marten
    • , Vincent Laville
    • , Maris Alver
    • , Evangelos Evangelou
    • , Maria E. Graff
    • , Meian He
    • , Brigitte Kühnel
    • , Leo-Pekka Lyytikäinen
    • , Pedro Marques-Vidal
    • , Ilja M. Nolte
    • , Nicholette D. Palmer
    • , Rainer Rauramaa
    • , Xiao-Ou Shu
    • , Harold Snieder
    • , Stefan Weiss
    • , Wanqing Wen
    • , Lisa R. Yanek
    • , Correa Adolfo
    • , Christie Ballantyne
    • , Larry Bielak
    • , Nienke R. Biermasz
    • , Eric Boerwinkle
    • , Niki Dimou
    • , Gudny Eiriksdottir
    • , Chuan Gao
    • , Sina A. Gharib
    • , Daniel J. Gottlieb
    • , José Haba-Rubio
    • , Tamara B. Harris
    • , Sami Heikkinen
    • , Raphaël Heinzer
    • , James E. Hixson
    • , Georg Homuth
    • , M. Arfan Ikram
    • , Pirjo Komulainen
    • , Jose E. Krieger
    • , Jiwon Lee
    • , Jingmin Liu
    • , Kurt K. Lohman
    • , Annemarie I. Luik
    • , Reedik Mägi
    • , Lisa W. Martin
    • , Thomas Meitinger
    • , Andres Metspalu
    • , Yuri Milaneschi
    • , Mike A. Nalls
    • , Jeff O’Connell
    • , Annette Peters
    • , Patricia Peyser
    • , Olli T. Raitakari
    • , Alex P. Reiner
    • , Patrick C. N. Rensen
    • , Treva K. Rice
    • , Stephen S. Rich
    • , Till Roenneberg
    • , Jerome I. Rotter
    • , Pamela J. Schreiner
    • , James Shikany
    • , Stephen S. Sidney
    • , Mario Sims
    • , Colleen M. Sitlani
    • , Tamar Sofer
    • , Konstantin Strauch
    • , Morris A. Swertz
    • , Kent D. Taylor
    • , André G. Uitterlinden
    • , Cornelia M. van Duijn
    • , Henry Völzke
    • , Melanie Waldenberger
    • , Robert B. Wallance
    • , Ko Willems van Dijk
    • , Caizheng Yu
    • , Alan B. Zonderman
    • , Diane M. Becker
    • , Paul Elliott
    • , Tõnu Esko
    • , Christian Gieger
    • , Hans J. Grabe
    • , Timo A. Lakka
    • , Terho Lehtimäki
    • , Kari E. North
    • , Brenda W. J. H. Penninx
    • , Peter Vollenweider
    • , Lynne E. Wagenknecht
    • , Tangchun Wu
    • , Yong-Bing Xiang
    • , Wei Zheng
    • , Donna K. Arnett
    • , Claude Bouchard
    • , Michele K. Evans
    • , Vilmundur Gudnason
    • , Sharon Kardia
    • , Tanika N. Kelly
    • , Stephen B. Kritchevsky
    • , Ruth J. F. Loos
    • , Alexandre C. Pereira
    • , Mike Province
    • , Bruce M. Psaty
    • , Charles Rotimi
    • , Xiaofeng Zhu
    • , Najaf Amin
    • , L. Adrienne Cupples
    • , Myriam Fornage
    • , Ervin F. Fox
    • , Xiuqing Guo
    • , W. James Gauderman
    • , Kenneth Rice
    • , Charles Kooperberg
    • , Patricia B. Munroe
    • , Ching-Ti Liu
    • , Alanna C. Morrison
    • , Dabeeru C. Rao
    • , Diana van Heemst
    •  & Susan Redline
  • Article
    | Open Access

    Immune cells contribute to the aortic wall destruction during abdominal aortic aneurysm (AAA) development. Here, Peshkova et al. show that cytokine signaling through interleukin-27 receptor is required for Angiotensin II-induced myelopoiesis and mature myeloid cells production, thus contributing to their aortic accumulation and aneurysm progression

    • Iuliia O. Peshkova
    • , Turan Aghayev
    • , Aliia R. Fatkhullina
    • , Petr Makhov
    • , Elizaveta K. Titerina
    • , Satoru Eguchi
    • , Yin Fei Tan
    • , Andrew V. Kossenkov
    • , Marina V. Khoreva
    • , Lyudmila V. Gankovskaya
    • , Stephen M. Sykes
    •  & Ekaterina K. Koltsova
  • Article
    | Open Access

    The endothelium actively maintains an anticoagulant surface through expression of thrombomodulin. Here, Peghaire et al. identify an anti-thrombotic pathway that controls thrombomodulin expression selectively in regions of low shear stress, via cooperation of the transcription factors ERG and KLF2.

    • C. Peghaire
    • , N. P. Dufton
    • , M. Lang
    • , I. I. Salles-Crawley
    • , J. Ahnström
    • , V. Kalna
    • , C. Raimondi
    • , C. Pericleous
    • , L. Inuabasi
    • , R. Kiseleva
    • , V. R. Muzykantov
    • , J. C. Mason
    • , G. M. Birdsey
    •  & A. M. Randi
  • Article
    | Open Access

    Mutations associated with SCN5A, which encodes the major cardiac sodium channel, influence impulse conduction and are associated with arrhythmia disorders. Here, the authors identify an evolutionary conserved, super enhancer-like, regulatory cluster downstream of SCN5A and show that it controls the chromatin architecture of the locus and Scn5a expression.

    • Joyce C. K. Man
    • , Rajiv A. Mohan
    • , Malou van den Boogaard
    • , Catharina R. E. Hilvering
    • , Catherine Jenkins
    • , Vincent Wakker
    • , Valerio Bianchi
    • , Wouter de Laat
    • , Phil Barnett
    • , Bastiaan J. Boukens
    •  & Vincent M. Christoffels
  • Article
    | Open Access

    Many patients, following therapy for acute myocardial infarction, develop adverse cardiac remodelling. Here the authors present injectable recombinant human collagen 10 of 10 type I and III matrices that are able to limit adverse remodelling and improve function of the myocardium.

    • Sarah McLaughlin
    • , Brian McNeill
    • , James Podrebarac
    • , Katsuhiro Hosoyama
    • , Veronika Sedlakova
    • , Gregory Cron
    • , David Smyth
    • , Richard Seymour
    • , Keshav Goel
    • , Wenbin Liang
    • , Katey J. Rayner
    • , Marc Ruel
    • , Erik J. Suuronen
    •  & Emilio I. Alarcon
  • Article
    | Open Access

    Aberrant morphology of the QRS complex in an electrocardiogram can be associated with cardiac morbidity and mortality. Here, the authors perform genome-wide association studies for ten measures of the QRS complex in 81,192 individuals and find 86 previously unreported loci that associate with at least one parameter.

    • Kristjan Norland
    • , Gardar Sveinbjornsson
    • , Rosa B. Thorolfsdottir
    • , Olafur B. Davidsson
    • , Vinicius Tragante
    • , Sridharan Rajamani
    • , Anna Helgadottir
    • , Solveig Gretarsdottir
    • , Jessica van Setten
    • , Folkert W. Asselbergs
    • , Jon Th. Sverrisson
    • , Sigurdur S. Stephensen
    • , Gylfi Oskarsson
    • , Emil L. Sigurdsson
    • , Karl Andersen
    • , Ragnar Danielsen
    • , Gudmundur Thorgeirsson
    • , Unnur Thorsteinsdottir
    • , David O. Arnar
    • , Patrick Sulem
    • , Hilma Holm
    • , Daniel F. Gudbjartsson
    •  & Kari Stefansson
  • Article
    | Open Access

    Genome-wide association studies of metabolites have revealed hundreds of genetic associations using univariate analyses. Here, the authors use a multivariate approach to perform association analyses for 158 serum metabolites, followed by fine mapping and GxE interaction tests with statin use and age.

    • Apolline Gallois
    • , Joel Mefford
    • , Arthur Ko
    • , Amaury Vaysse
    • , Hanna Julienne
    • , Mika Ala-Korpela
    • , Markku Laakso
    • , Noah Zaitlen
    • , Päivi Pajukanta
    •  & Hugues Aschard
  • Article
    | Open Access

    The majority of disease-associated genetic variants lie in non-coding regions. Here the authors generated and compiled human transcriptomic, epigenomic and chromatin conformation datasets, to identify genes associated with atrial fibrillation and functional non-coding variants.

    • Antoinette F. van Ouwerkerk
    • , Fernanda M. Bosada
    • , Karel van Duijvenboden
    • , Matthew C. Hill
    • , Lindsey E. Montefiori
    • , Koen T. Scholman
    • , Jia Liu
    • , Antoine A. F. de Vries
    • , Bastiaan J. Boukens
    • , Patrick T. Ellinor
    • , Marie José T. H. Goumans
    • , Igor R. Efimov
    • , Marcelo A. Nobrega
    • , Phil Barnett
    • , James F. Martin
    •  & Vincent M. Christoffels
  • Article
    | Open Access

    Large whole-exome sequencing studies have suggested that the genetic architecture of syndromic congenital heart disease (CHD) is different from sporadic forms. Here, Watkins et al. estimate the relative contribution of damaging recessive and de novo genotypes to CHD in 2391 trios and find them to be associated with different gene functions.

    • W. Scott Watkins
    • , E. Javier Hernandez
    • , Sergiusz Wesolowski
    • , Brent W. Bisgrove
    • , Ryan T. Sunderland
    • , Edwin Lin
    • , Gordon Lemmon
    • , Bradley L. Demarest
    • , Thomas A. Miller
    • , Daniel Bernstein
    • , Martina Brueckner
    • , Wendy K. Chung
    • , Bruce D. Gelb
    • , Elizabeth Goldmuntz
    • , Jane W. Newburger
    • , Christine E. Seidman
    • , Yufeng Shen
    • , H. Joseph Yost
    • , Mark Yandell
    •  & Martin Tristani-Firouzi
  • Article
    | Open Access

    Mutations in the gene HADHA result in mitochondrial tri-functional protein (MTP) deficiency and can result in sudden infant death syndrome for which there is no treatment. Here the authors show that the MTP deficient pathology in human cardiomyocytes leads to an abnormal cardiolipin pattern and suggests that cardiolipin affecting compounds may serve as a potential therapy.

    • Jason W. Miklas
    • , Elisa Clark
    • , Shiri Levy
    • , Damien Detraux
    • , Andrea Leonard
    • , Kevin Beussman
    • , Megan R. Showalter
    • , Alec T. Smith
    • , Peter Hofsteen
    • , Xiulan Yang
    • , Jesse Macadangdang
    • , Tuula Manninen
    • , Daniel Raftery
    • , Anup Madan
    • , Anu Suomalainen
    • , Deok-Ho Kim
    • , Charles E. Murry
    • , Oliver Fiehn
    • , Nathan J. Sniadecki
    • , Yuliang Wang
    •  & Hannele Ruohola-Baker
  • Article
    | Open Access

    The lymphatic vasculature is essential to maintain fluid homeostasis and immune surveillance, including in the brain where lymphatic vessels were only recently identified. Here, Jacob et al. provide an anatomical map of lymphatic vessels in the vertebral column, where they find these contribute to fluid drainage and immune responses.

    • Laurent Jacob
    • , Ligia Simoes Braga Boisserand
    • , Luiz Henrique Medeiros Geraldo
    • , Jose de Brito Neto
    • , Thomas Mathivet
    • , Salli Antila
    • , Besma Barka
    • , Yunling Xu
    • , Jean-Mickael Thomas
    • , Juliette Pestel
    • , Marie-Stéphane Aigrot
    • , Eric Song
    • , Harri Nurmi
    • , Seyoung Lee
    • , Kari Alitalo
    • , Nicolas Renier
    • , Anne Eichmann
    •  & Jean-Leon Thomas
  • Article
    | Open Access

    Myofibroblast differentiation contributes to extracellular matrix remodeling and fibrosis. Here, the authors report that alterations in mitochondrial calcium uptake is essential for metabolic reprogramming and epigenetic signaling for activation of the myofibroblast gene program.

    • Alyssa A. Lombardi
    • , Andrew A. Gibb
    • , Ehtesham Arif
    • , Devin W. Kolmetzky
    • , Dhanendra Tomar
    • , Timothy S. Luongo
    • , Pooja Jadiya
    • , Emma K. Murray
    • , Pawel K. Lorkiewicz
    • , György Hajnóczky
    • , Elizabeth Murphy
    • , Zoltan P. Arany
    • , Daniel P. Kelly
    • , Kenneth B. Margulies
    • , Bradford G. Hill
    •  & John W. Elrod
  • Article
    | Open Access

    Both insulin and IGF-1 signaling have been implicated in arterial intimal hyperplasia. Here the authors dissect the relative contributions of insulin and IGF-1 receptors, showing that homodimers of insulin receptors, but not IGF-1 receptor, induce proliferation of vascular smooth muscle cells.

    • Qian Li
    • , Jialin Fu
    • , Yu Xia
    • , Weier Qi
    • , Atsushi Ishikado
    • , Kyoungmin Park
    • , Hisashi Yokomizo
    • , Qian Huang
    • , Weikang Cai
    • , Christian Rask-Madsen
    • , C. Ronald Kahn
    •  & George L. King
  • Article
    | Open Access

    Cardiovascular diseases (CVD) are associated with plasma lipid levels. Here, Tabassum et al. perform genome-wide association studies for lipidomic profiles with 141 (non-standard) lipid species which highlights shared genetic loci with CVD and that traditional lipids have low genetic correlation with other lipids.

    • Rubina Tabassum
    • , Joel T. Rämö
    • , Pietari Ripatti
    • , Jukka T. Koskela
    • , Mitja Kurki
    • , Juha Karjalainen
    • , Priit Palta
    • , Shabbeer Hassan
    • , Javier Nunez-Fontarnau
    • , Tuomo T. J. Kiiskinen
    • , Sanni Söderlund
    • , Niina Matikainen
    • , Mathias J. Gerl
    • , Michal A. Surma
    • , Christian Klose
    • , Nathan O. Stitziel
    • , Hannele Laivuori
    • , Aki S. Havulinna
    • , Susan K. Service
    • , Veikko Salomaa
    • , Matti Pirinen
    • , Anu Jalanko
    • , Jaakko Kaprio
    • , Kati Donner
    • , Mari Kaunisto
    • , Nina Mars
    • , Alexander Dada
    • , Anastasia Shcherban
    • , Andrea Ganna
    • , Arto Lehisto
    • , Elina Kilpeläinen
    • , Georg Brein
    • , Ghazal Awaisa
    • , Jarmo Harju
    • , Kalle Pärn
    • , Pietro Della Briotta Parolo
    • , Risto Kajanne
    • , Susanna Lemmelä
    • , Timo P. Sipilä
    • , Tuomas Sipilä
    • , Ulrike Lyhs
    • , Vincent Llorens
    • , Teemu Niiranen
    • , Kati Kristiansson
    • , Lotta Männikkö
    • , Manuel González Jiménez
    • , Markus Perola
    • , Regis Wong
    • , Terhi Kilpi
    • , Tero Hiekkalinna
    • , Elina Järvensivu
    • , Essi Kaiharju
    • , Hannele Mattsson
    • , Markku Laukkanen
    • , Päivi Laiho
    • , Sini Lähteenmäki
    • , Tuuli Sistonen
    • , Sirpa Soini
    • , Adam Ziemann
    • , Anne Lehtonen
    • , Apinya Lertratanakul
    • , Bob Georgantas
    • , Bridget Riley-Gillis
    • , Danjuma Quarless
    • , Fedik Rahimov
    • , Graham Heap
    • , Howard Jacob
    • , Jeffrey Waring
    • , Justin Wade Davis
    • , Nizar Smaoui
    • , Relja Popovic
    • , Sahar Esmaeeli
    • , Jeff Waring
    • , Athena Matakidou
    • , Ben Challis
    • , David Close
    • , Slavé Petrovski
    • , Antti Karlsson
    • , Johanna Schleutker
    • , Kari Pulkki
    • , Petri Virolainen
    • , Lila Kallio
    • , Arto Mannermaa
    • , Sami Heikkinen
    • , Veli-Matti Kosma
    • , Chia-Yen Chen
    • , Heiko Runz
    • , Jimmy Liu
    • , Paola Bronson
    • , Sally John
    • , Sanni Lahdenperä
    • , Susan Eaton
    • , Wei Zhou
    • , Minna Hendolin
    • , Outi Tuovila
    • , Raimo Pakkanen
    • , Joseph Maranville
    • , Keith Usiskin
    • , Marla Hochfeld
    • , Robert Plenge
    • , Robert Yang
    • , Shameek Biswas
    • , Steven Greenberg
    • , Eija Laakkonen
    • , Juha Kononen
    • , Juha Paloneva
    • , Urho Kujala
    • , Teijo Kuopio
    • , Jari Laukkanen
    • , Eeva Kangasniemi
    • , Kimmo Savinainen
    • , Reijo Laaksonen
    • , Mikko Arvas
    • , Jarmo Ritari
    • , Jukka Partanen
    • , Kati Hyvärinen
    • , Tiina Wahlfors
    • , Andrew Peterson
    • , Danny Oh
    • , Diana Chang
    • , Edmond Teng
    • , Erich Strauss
    • , Geoff Kerchner
    • , Hao Chen
    • , Hubert Chen
    • , Jennifer Schutzman
    • , John Michon
    • , Julie Hunkapiller
    • , Mark McCarthy
    • , Natalie Bowers
    • , Tim Lu
    • , Tushar Bhangale
    • , David Pulford
    • , Dawn Waterworth
    • , Diptee Kulkarni
    • , Fanli Xu
    • , Jo Betts
    • , Jorge Esparza Gordillo
    • , Joshua Hoffman
    • , Kirsi Auro
    • , Linda McCarthy
    • , Soumitra Ghosh
    • , Meg Ehm
    • , Kimmo Pitkänen
    • , Tomi Mäkelä
    • , Anu Loukola
    • , Heikki Joensuu
    • , Juha Sinisalo
    • , Kari Eklund
    • , Lauri Aaltonen
    • , Martti Färkkilä
    • , Olli Carpen
    • , Paula Kauppi
    • , Pentti Tienari
    • , Terhi Ollila
    • , Tiinamaija Tuomi
    • , Tuomo Meretoja
    • , Anne Pitkäranta
    • , Joni Turunen
    • , Katariina Hannula-Jouppi
    • , Sampsa Pikkarainen
    • , Sanna Seitsonen
    • , Miika Koskinen
    • , Antti Palomäki
    • , Juha Rinne
    • , Kaj Metsärinne
    • , Klaus Elenius
    • , Laura Pirilä
    • , Leena Koulu
    • , Markku Voutilainen
    • , Markus Juonala
    • , Sirkku Peltonen
    • , Vesa Aaltonen
    • , Andrey Loboda
    • , Anna Podgornaia
    • , Aparna Chhibber
    • , Audrey Chu
    • , Caroline Fox
    • , Dorothee Diogo
    • , Emily Holzinger
    • , John Eicher
    • , Padhraig Gormley
    • , Vinay Mehta
    • , Xulong Wang
    • , Johannes Kettunen
    • , Katri Pylkäs
    • , Marita Kalaoja
    • , Minna Karjalainen
    • , Reetta Hinttala
    • , Riitta Kaarteenaho
    • , Seppo Vainio
    • , Tuomo Mantere
    • , Seppo Vainio
    • , Anne Remes
    • , Johanna Huhtakangas
    • , Juhani Junttila
    • , Kaisa Tasanen
    • , Laura Huilaja
    • , Marja Luodonpää
    • , Nina Hautala
    • , Peeter Karihtala
    • , Saila Kauppila
    • , Terttu Harju
    • , Timo Blomster
    • , Hilkka Soininen
    • , Ilkka Harvima
    • , Jussi Pihlajamäki
    • , Kai Kaarniranta
    • , Margit Pelkonen
    • , Markku Laakso
    • , Mikko Hiltunen
    • , Mikko Kiviniemi
    • , Oili Kaipiainen-Seppänen
    • , Päivi Auvinen
    • , Reetta Kälviäinen
    • , Valtteri Julkunen
    • , Anders Malarstig
    • , Åsa Hedman
    • , Catherine Marshall
    • , Christopher Whelan
    • , Heli Lehtonen
    • , Jaakko Parkkinen
    • , Kari Linden
    • , Kirsi Kalpala
    • , Melissa Miller
    • , Nan Bing
    • , Stefan McDonough
    • , Xing Chen
    • , Xinli Hu
    • , Ying Wu
    • , Annika Auranen
    • , Airi Jussila
    • , Hannele Uusitalo-Järvinen
    • , Hannu Kankaanranta
    • , Hannu Uusitalo
    • , Jukka Peltola
    • , Mika Kähönen
    • , Pia Isomäki
    • , Tarja Laitinen
    • , Teea Salmi
    • , Anthony Muslin
    • , Clarence Wang
    • , Clement Chatelain
    • , Ethan Xu
    • , Franck Auge
    • , Kathy Call
    • , Kathy Klinger
    • , Marika Crohns
    • , Matthias Gossel
    • , Kimmo Palin
    • , Manuel Rivas
    • , Harri Siirtola
    • , Javier Gracia Tabuenca
    • , Matti Jauhiainen
    • , Mark J. Daly
    • , Nelson B. Freimer
    • , Aarno Palotie
    • , Marja-Riitta Taskinen
    • , Kai Simons
    •  & Samuli Ripatti
  • Article
    | Open Access

    The majority of published GWAS was performed in European ancestry populations. Here, Kuchenbaecker et al., test to which extent lipid loci are shared and find that the major lipid loci are mostly transferrable between Europeans and Asians while there are notable exceptions for African populations.

    • Karoline Kuchenbaecker
    • , Nikita Telkar
    • , Theresa Reiker
    • , Robin G. Walters
    • , Kuang Lin
    • , Anders Eriksson
    • , Deepti Gurdasani
    • , Arthur Gilly
    • , Lorraine Southam
    • , Emmanouil Tsafantakis
    • , Maria Karaleftheri
    • , Janet Seeley
    • , Anatoli Kamali
    • , Gershim Asiki
    • , Iona Y. Millwood
    • , Michael Holmes
    • , Huaidong Du
    • , Yu Guo
    • , Meena Kumari
    • , George Dedoussis
    • , Liming Li
    • , Zhengming Chen
    • , Manjinder S. Sandhu
    • , Eleftheria Zeggini
    • , Michaela Benzeval
    • , Jonathan Burton
    • , Nicholas Buck
    • , Annette Jäckle
    • , Heather Laurie
    • , Peter Lynn
    • , Stephen Pudney
    • , Birgitta Rabe
    •  & Dieter Wolke
  • Article
    | Open Access

    Circular RNAs (circRNAs) are non-coding RNAs generated from pre-mRNAs of coding genes by the splicing machinery whose function in the heart is poorly understood. Here the authors show that AAV-mediated delivery of the circRNA circFndc3b prevents cardiomyocyte apoptosis, enhances angiogenesis, and attenuates LV dysfunction post-MI in mice by regulating FUS-VEGF-A signalling.

    • Venkata Naga Srikanth Garikipati
    • , Suresh Kumar Verma
    • , Zhongjian Cheng
    • , Dongming Liang
    • , May M. Truongcao
    • , Maria Cimini
    • , Yujia Yue
    • , Grace Huang
    • , Chunlin Wang
    • , Cindy Benedict
    • , Yan Tang
    • , Vandana Mallaredy
    • , Jessica Ibetti
    • , Laurel Grisanti
    • , Sarah M. Schumacher
    • , Erhe Gao
    • , Sudarsan Rajan
    • , Jeremy E. Wilusz
    • , David Goukassian
    • , Steven R. Houser
    • , Walter J. Koch
    •  & Raj Kishore
  • Article
    | Open Access

    Differentially methylated CpGs can inform on disease mechanisms and be useful as biomarkers. Here, the authors perform GWAS for DNA methylation in whole blood, cis- and trans-meQTL mapping, followed by Mendelian randomization analysis that links meQTLs with cardiovascular diseases.

    • Tianxiao Huan
    • , Roby Joehanes
    • , Ci Song
    • , Fen Peng
    • , Yichen Guo
    • , Michael Mendelson
    • , Chen Yao
    • , Chunyu Liu
    • , Jiantao Ma
    • , Melissa Richard
    • , Golareh Agha
    • , Weihua Guan
    • , Lynn M. Almli
    • , Karen N. Conneely
    • , Joshua Keefe
    • , Shih-Jen Hwang
    • , Andrew D. Johnson
    • , Myriam Fornage
    • , Liming Liang
    •  & Daniel Levy
  • Article
    | Open Access

    Stress kinases are activated in peripheral ischemic tissues in the presence of vascular diseases. Here the authors show that inhibition of the neural JNK3 kinase improves recovery from hind limb ischemia in animals through activation of the transcription factors Egr1/Creb1 and upregulation of growth factors.

    • Shashi Kant
    • , Siobhan M. Craige
    • , Kai Chen
    • , Michaella M. Reif
    • , Heather Learnard
    • , Mark Kelly
    • , Amada D. Caliz
    • , Khanh-Van Tran
    • , Kasmir Ramo
    • , Owen M. Peters
    • , Marc Freeman
    • , Roger J. Davis
    •  & John F. Keaney Jr.
  • Article
    | Open Access

    Renin-angiotensin system inhibitors (RASi) are beneficial in several classes of cardiovascular patients. However, whether their perioperative use is beneficial and/or safe in cardiac surgery is unclear. Here the authors perform a multicenter retrospective cohort study showing that preoperative and postoperative use of RASi is associated with reduction of mortality in patients undergoing cardiac surgery.

    • Qian Ding
    • , Zugui Zhang
    • , Hong Liu
    • , Huang Nie
    • , Mark Berguson
    • , Jordan E. Goldhammer
    • , Nilas Young
    • , Douglas Boyd
    • , Rohinton Morris
    •  & Jianzhong Sun
  • Article
    | Open Access

    Survival and proliferation of vascular cells in the presence of DNA damage is a characteristic of pulmonary arterial hypertension. Here the authors show that the phosphatase EYA3 contributes to vascular remodeling by promoting survival of damaged cells, and present results of genetic and pharmacological EYA3 inhibition.

    • Yuhua Wang
    • , Ram Naresh Pandey
    • , Allen J. York
    • , Jaya Mallela
    • , William C. Nichols
    • , Yueh-Chiang Hu
    • , Jeffery D. Molkentin
    • , Kathryn A. Wikenheiser-Brokamp
    •  & Rashmi S. Hegde
  • Article
    | Open Access

    Na+-H+ exchanger 1 (Nhe1) regulates extracellular pH by extruding protons in exchange for extracellular Na+ . Here, Liu et al. show that Nhe1 promotes the development and acidification of atherosclerotic lesions and that pH-sensitive probes can be used to monitor plaque growth and acidification.

    • Cong-Lin Liu
    • , Xian Zhang
    • , Jing Liu
    • , Yunzhe Wang
    • , Galina K. Sukhova
    • , Gregory R. Wojtkiewicz
    • , Tianxiao Liu
    • , Rui Tang
    • , Samuel Achilefu
    • , Matthias Nahrendorf
    • , Peter Libby
    • , Junli Guo
    • , Jin-Ying Zhang
    •  & Guo-Ping Shi
  • Article
    | Open Access

    The plasma metalloprotease ADAMTS13 regulates the platelet-tethering function of von Willebrand factor (VWF) in a shear-dependent manner. Here the authors present the ADAMTS13 crystal structure of the 70kDa N-terminal metalloprotease to spacer domains, and using kinetic measurements they identify a substrate binding induced allosteric mechanism for ADAMTS13, where VWF functions both as an activating cofactor and substrate.

    • Anastasis Petri
    • , Hyo Jung Kim
    • , Yaoxian Xu
    • , Rens de Groot
    • , Chan Li
    • , Aline Vandenbulcke
    • , Karen Vanhoorelbeke
    • , Jonas Emsley
    •  & James T. B. Crawley
  • Article
    | Open Access

    The studies showing health benefits of flavonoids and their impact on cancer mortality are incomplete. Here, the authors perform a prospective cohort study in Danish participants and demonstrate an inverse association between regular flavonoid intake and both cardiovascular and cancer related mortality.

    • Nicola P. Bondonno
    • , Frederik Dalgaard
    • , Cecilie Kyrø
    • , Kevin Murray
    • , Catherine P. Bondonno
    • , Joshua R. Lewis
    • , Kevin D. Croft
    • , Gunnar Gislason
    • , Augustin Scalbert
    • , Aedin Cassidy
    • , Anne Tjønneland
    • , Kim Overvad
    •  & Jonathan M. Hodgson
  • Article
    | Open Access

    Levels of sodium and potassium in urine are associated with cardiovascular traits. Here, Pazoki et al. perform genome-wide association studies for urinary sodium and potassium secretion and identify 50 and 13 novel loci, respectively, some of which show a potential causal relationship with blood pressure based on MR analysis.

    • Raha Pazoki
    • , Evangelos Evangelou
    • , David Mosen-Ansorena
    • , Rui Climaco Pinto
    • , Ibrahim Karaman
    • , Paul Blakeley
    • , Dipender Gill
    • , Verena Zuber
    • , Paul Elliott
    • , Ioanna Tzoulaki
    •  & Abbas Dehghan
  • Article
    | Open Access

    Pathological cardiac fibrosis is a hallmark of diseases leading to heart failure. Here, the authors used systems genetics to identify a pro-fibrotic gene network regulated by WWP2, a E3 ubiquitin ligase, which orchestrates the nucleocytoplasmic shuttling and transcriptional activity of SMAD2 in the diseased heart.

    • Huimei Chen
    • , Aida Moreno-Moral
    • , Francesco Pesce
    • , Nithya Devapragash
    • , Massimiliano Mancini
    • , Ee Ling Heng
    • , Maxime Rotival
    • , Prashant K. Srivastava
    • , Nathan Harmston
    • , Kirill Shkura
    • , Owen J. L. Rackham
    • , Wei-Ping Yu
    • , Xi-Ming Sun
    • , Nicole Gui Zhen Tee
    • , Elisabeth Li Sa Tan
    • , Paul J. R. Barton
    • , Leanne E. Felkin
    • , Enrique Lara-Pezzi
    • , Gianni Angelini
    • , Cristina Beltrami
    • , Michal Pravenec
    • , Sebastian Schafer
    • , Leonardo Bottolo
    • , Norbert Hubner
    • , Costanza Emanueli
    • , Stuart A. Cook
    •  & Enrico Petretto
  • Article
    | Open Access

    Vascular remodelling contributes to the development of pulmonary hypertension (PH). Here Luo and colleagues find that increases in CD146 levels drive vascular remodelling in PH through a cross-talk with hypoxia inducible factor (HIF) signalling, and show that inhibition of CD146 can attenuate disease progression.

    • Yongting Luo
    • , Xiao Teng
    • , Lingling Zhang
    • , Jianan Chen
    • , Zheng Liu
    • , Xuehui Chen
    • , Shuai Zhao
    • , Sai Yang
    • , Jing Feng
    •  & Xiyun Yan
  • Article
    | Open Access

    Individuals carrying a gain-of-function mutation in PKG1 develop thoracic aortic aneurysms and dissections. Here Schwaerzer et al. show that mice carrying the same mutation recapitulate the human disease, and find that treatment with anti-oxidants including cobinamide, a vitamin B12 analog, prevents disease progression.

    • Gerburg K. Schwaerzer
    • , Hema Kalyanaraman
    • , Darren E. Casteel
    • , Nancy D. Dalton
    • , Yusu Gu
    • , Seunghoe Lee
    • , Shunhui Zhuang
    • , Nisreen Wahwah
    • , Jan M. Schilling
    • , Hemal H. Patel
    • , Qian Zhang
    • , Ayako Makino
    • , Dianna M. Milewicz
    • , Kirk L. Peterson
    • , Gerry R. Boss
    •  & Renate B. Pilz
  • Article
    | Open Access

    There are few studies of structural changes in ascending and descending sensorimotor pathways after stroke, beyond the corticospinal tract, in the brain. Here the authors identify changes in white matter structure in brainstem and spinal cord following stroke, and show its relationship to motor impairment.

    • Haleh Karbasforoushan
    • , Julien Cohen-Adad
    •  & Julius P. A. Dewald
  • Article
    | Open Access

    Memory is hypothesised to depend on different brain regions that interact in a network. Here, the authors use case studies of stroke patients with amnesia from the literature to identify brain regions that are part of this network.

    • Michael A. Ferguson
    • , Chun Lim
    • , Danielle Cooke
    • , R. Ryan Darby
    • , Ona Wu
    • , Natalia S. Rost
    • , Maurizio Corbetta
    • , Jordan Grafman
    •  & Michael D. Fox
  • Article
    | Open Access

    Atherosclerosis results from the accumulation of lipoproteins in the vascular wall. Here, Thierer et al. report the design of a chemiluminescent reporter for atherogenic lipoproteins using fusion of apolipoprotein-B to a luciferase enzyme, and find it bears potential for the identification of regulators of lipoprotein metabolism in vivo.

    • James H. Thierer
    • , Stephen C. Ekker
    •  & Steven A. Farber
  • Article
    | Open Access

    The depolarizing funny current contributing to cardiac pacemaking is upregulated in the myocardium of  failing and infarcted hearts, but whether the current is implied in disease mechanisms is unclear. Here the authors generate HCN4 transgenic mice and show that upregulation of funny current to the levels observed in human heart failure alters calcium homeostasis leading to cardiac remodelling and arrhythmia.

    • Pessah Yampolsky
    • , Michael Koenen
    • , Matias Mosqueira
    • , Pascal Geschwill
    • , Sebastian Nauck
    • , Monika Witzenberger
    • , Claudia Seyler
    • , Thomas Fink
    • , Mathieu Kruska
    • , Claus Bruehl
    • , Alexander P. Schwoerer
    • , Heimo Ehmke
    • , Rainer H. A. Fink
    • , Andreas Draguhn
    • , Dierk Thomas
    • , Hugo A. Katus
    •  & Patrick A. Schweizer
  • Article
    | Open Access

    How coronary vessels develop and respond to injury is not fully understood. Here, the authors use murine enhancer:reporter models to identify three transcriptional pathways active in different parts of coronary vasculature. These also contribute to neovascularization in the injured neonatal, but not adult, heart.

    • Sophie Payne
    • , Mala Gunadasa-Rohling
    • , Alice Neal
    • , Andia N. Redpath
    • , Jyoti Patel
    • , Kira M. Chouliaras
    • , Indrika Ratnayaka
    • , Nicola Smart
    •  & Sarah De Val
  • Article
    | Open Access

    Thoracic aortic dissection has a high fatality rate and no effective treatment. Here, the authors develop cationic nanoparticles for the delivery of miR-145 and show that they stabilize vascular structures and prevent further deterioration of the aorta in mouse models of the disease.

    • Chen Xu
    • , Yanzhenzi Zhang
    • , Ke Xu
    • , Jing-Jun Nie
    • , Bingran Yu
    • , Sijin Li
    • , Gang Cheng
    • , Yulin Li
    • , Jie Du
    •  & Fu-Jian Xu
  • Article
    | Open Access

    The availability of labelled training data is one of the practical obstacles towards wide application of machine learning models in medicine. Here the authors develop a weakly supervised deep learning model for the classification of aortic malformations using unlabelled cardiac MRI sequences from the UK biobank.

    • Jason A. Fries
    • , Paroma Varma
    • , Vincent S. Chen
    • , Ke Xiao
    • , Heliodoro Tejeda
    • , Priyanka Saha
    • , Jared Dunnmon
    • , Henry Chubb
    • , Shiraz Maskatia
    • , Madalina Fiterau
    • , Scott Delp
    • , Euan Ashley
    • , Christopher Ré
    •  & James R. Priest
  • Article
    | Open Access

    Bioengineering of small diameter vascular grafts that recapitulate the features of native vessels is extremely challenging. Here the authors present a combined dip-spinning and blow-spinning technology to fabricate multi-layered cell-embedded grafts with native mechanical properties.

    • Tamara L. Akentjew
    • , Claudia Terraza
    • , Cristian Suazo
    • , Jekaterina Maksimcuka
    • , Camila A. Wilkens
    • , Francisco Vargas
    • , Gabriela Zavala
    • , Macarena Ocaña
    • , Javier Enrione
    • , Claudio M. García-Herrera
    • , Loreto M. Valenzuela
    • , Jonny J. Blaker
    • , Maroun Khoury
    •  & Juan Pablo Acevedo
  • Article
    | Open Access

    FHR1 is a serum protein implicated in complement regulation. Here the authors show that human FHR1 binds to necrotic cells, triggering inflammasome activation in monocytes in culture, localizes to necrotic tissue and correlates with inflammatory cytokine levels in vasculopathies.

    • Sarah Irmscher
    • , Silke R. Brix
    • , Svante L. H. Zipfel
    • , Luke D. Halder
    • , Sibel Mutlutürk
    • , Sonia Wulf
    • , Evaldas Girdauskas
    • , Hermann Reichenspurner
    • , Rolf A. K. Stahl
    • , Berit Jungnickel
    • , Thorsten Wiech
    • , Peter F. Zipfel
    •  & Christine Skerka
  • Article
    | Open Access

    Depression and transient ischaemic attacks are tightly regulated but the neural circuits underlying depression-modulated ischaemic injury are not known. Here, the authors show that the locus coeruleus-CA1 pathway is involved in depression-associated ischaemia susceptibility.

    • Qian Zhang
    • , Dian Xing Hu
    • , Feng He
    • , Chun Yang Li
    • , Guang Jian Qi
    • , Hong Wei Cai
    • , Tong Xia Li
    • , Jie Ming
    • , Pei Zhang
    • , Xiao Qian Chen
    •  & Bo Tian
  • Article
    | Open Access

    NLRC5 is known for its role in inflammation and antigen presentation. Here Luan et al. find that NLRC5 protects mice from intimal hyperplasia following vascular injury, and regulates the response of vascular smooth muscle cells to injury through direct interaction with PPARγ.

    • Peipei Luan
    • , Weixia Jian
    • , Xu Xu
    • , Wenxin Kou
    • , Qing Yu
    • , Handan Hu
    • , Dali Li
    • , Wei Wang
    • , Mark W. Feinberg
    • , Jianhui Zhuang
    • , Yawei Xu
    •  & Wenhui Peng
  • Article
    | Open Access

    The sinus node generates rhythmic heartbeat but the molecular basis of pacemaking is still under debate. Here, the authors combine quantitative proteomics and single-nucleus transcriptomics to characterize the molecular composition of the sinus node and provide insights into the underpinnings of pacemaking.

    • Nora Linscheid
    • , Sunil Jit R. J. Logantha
    • , Pi Camilla Poulsen
    • , Shanzhuo Zhang
    • , Maren Schrölkamp
    • , Kristoffer Lihme Egerod
    • , Jonatan James Thompson
    • , Ashraf Kitmitto
    • , Gina Galli
    • , Martin J. Humphries
    • , Henggui Zhang
    • , Tune H. Pers
    • , Jesper Velgaard Olsen
    • , Mark Boyett
    •  & Alicia Lundby
  • Article
    | Open Access

    Fibrosis is a hallmark of several cardiac pathologies and its underlying mechanisms are still poorly defined. Here the authors show that macrophage hypoxia signaling following transverse aortic constriction in mice suppresses the activation of cardiac fibroblasts by secreting oncostatin M.

    • Hajime Abe
    • , Norihiko Takeda
    • , Takayuki Isagawa
    • , Hiroaki Semba
    • , Satoshi Nishimura
    • , Masaki Suimye Morioka
    • , Yu Nakagama
    • , Tatsuyuki Sato
    • , Katsura Soma
    • , Katsuhiro Koyama
    • , Masaki Wake
    • , Manami Katoh
    • , Masataka Asagiri
    • , Michael L. Neugent
    • , Jung-whan Kim
    • , Christian Stockmann
    • , Tomo Yonezawa
    • , Ryo Inuzuka
    • , Yasushi Hirota
    • , Koji Maemura
    • , Takeshi Yamashita
    • , Kinya Otsu
    • , Ichiro Manabe
    • , Ryozo Nagai
    •  & Issei Komuro
  • Article
    | Open Access

    Pericytes are perivascular cells essential for blood-brain barrier maintenance. Here Diéguez-Hurtado et al. show that depletion of the transcription factor RBPJ in pericytes affects their molecular identity and disturbs endothelial cell behaviour, inducing the formation of vascular lesions in the brain.

    • Rodrigo Diéguez-Hurtado
    • , Katsuhiro Kato
    • , Benedetto Daniele Giaimo
    • , Melina Nieminen-Kelhä
    • , Hendrik Arf
    • , Francesca Ferrante
    • , Marek Bartkuhn
    • , Tobias Zimmermann
    • , M. Gabriele Bixel
    • , Hanna M. Eilken
    • , Susanne Adams
    • , Tilman Borggrefe
    • , Peter Vajkoczy
    •  & Ralf H. Adams
  • Article
    | Open Access

    Cerebral cavernous malformation is a vascular disease characterized by capillary-venous cavernomas in the central nervous system. Here the authors show that cavernomas display benign tumor characteristics and originate from the clonal expansion of mutated endothelial progenitors which can attract surrounding wild-type cells, inducing their mesenchymal transition and leading to growth of the cavernoma.

    • Matteo Malinverno
    • , Claudio Maderna
    • , Abdallah Abu Taha
    • , Monica Corada
    • , Fabrizio Orsenigo
    • , Mariaelena Valentino
    • , Federica Pisati
    • , Carmela Fusco
    • , Paolo Graziano
    • , Monica Giannotta
    • , Qing Cissy Yu
    • , Yi Arial Zeng
    • , Maria Grazia Lampugnani
    • , Peetra U. Magnusson
    •  & Elisabetta Dejana
  • Article
    | Open Access

    The genetic and pathogenetic basis of heart failure is incompletely understood. Here, the authors present a high-fidelity tissue collection from rapidly preserved failing and non-failing control hearts which are used for eQTL mapping and network analysis, resulting in the prioritization of PPP1R3A as a heart failure gene.

    • Pablo Cordero
    • , Victoria N. Parikh
    • , Elizabeth T. Chin
    • , Ayca Erbilgin
    • , Michael J. Gloudemans
    • , Ching Shang
    • , Yong Huang
    • , Alex C. Chang
    • , Kevin S. Smith
    • , Frederick Dewey
    • , Kathia Zaleta
    • , Michael Morley
    • , Jeff Brandimarto
    • , Nicole Glazer
    • , Daryl Waggott
    • , Aleksandra Pavlovic
    • , Mingming Zhao
    • , Christine S. Moravec
    • , W. H. Wilson Tang
    • , Jamie Skreen
    • , Christine Malloy
    • , Sridhar Hannenhalli
    • , Hongzhe Li
    • , Scott Ritter
    • , Mingyao Li
    • , Daniel Bernstein
    • , Andrew Connolly
    • , Hakon Hakonarson
    • , Aldons J. Lusis
    • , Kenneth B. Margulies
    • , Anna A. Depaoli-Roach
    • , Stephen B. Montgomery
    • , Matthew T. Wheeler
    • , Thomas Cappola
    •  & Euan A. Ashley
  • Article
    | Open Access

    Hypertrophic cardiomyopathy (HCM) leads to hyper-contractility of the heart and is often caused by mutations in human β-cardiac myosin. Here authors show that four separate β-cardiac myosin mutations can modulate myosin activity by disrupting intramolecular interactions.

    • Arjun S. Adhikari
    • , Darshan V. Trivedi
    • , Saswata S. Sarkar
    • , Dan Song
    • , Kristina B. Kooiker
    • , Daniel Bernstein
    • , James A. Spudich
    •  & Kathleen M. Ruppel
  • Article
    | Open Access

    Men and women differ in their risk of developing coronary artery disease, in part due to differences in their levels of sex hormones. Here, AlSiraj et al. show that the XX sex genotype regulates lipid metabolism and promotes atherosclerosis independently of sex hormones in mice.

    • Yasir AlSiraj
    • , Xuqi Chen
    • , Sean E. Thatcher
    • , Ryan E. Temel
    • , Lei Cai
    • , Eric Blalock
    • , Wendy Katz
    • , Heba M. Ali
    • , Michael Petriello
    • , Pan Deng
    • , Andrew J. Morris
    • , Xuping Wang
    • , Aldons J. Lusis
    • , Arthur P. Arnold
    • , Karen Reue
    • , Katherine Thompson
    • , Patrick Tso
    •  & Lisa A. Cassis