Cardiology

  • Article
    | Open Access

    Atherosclerosis diagnosis relies primarily on imaging and early detection of high-risk atherosclerotic plaques is important for risk stratification of patients and stabilization therapies. Here Htun et al. demonstrate that vulnerable atherosclerotic plaques generate near-infrared autofluorescence that can be detected via emission computed tomography.

    • Nay Min Htun
    • , Yung Chih Chen
    •  & Karlheinz Peter
  • Article
    | Open Access

    H-type endothelium, defined by the high expression of CD31 and endomucin, is found in the bone where it promotes angiogenesis and osteogensis. Here Yanget al. show that the miR-497195 cluster regulates the generation and maintenance of the H-type endothelium by controlling the levels of Notch regulator Fbxw7 and the HIF regulator P4HTM.

    • Mi Yang
    • , Chang-Jun Li
    •  & Xiang-Hang Luo
  • Article
    | Open Access

    Heart rate variability (HRV) describes the individual variation in cardiac cycle duration and is a measure of vagal control of heart rate. Here, the authors identify seventeen single-nucleotide polymorphisms associated with HRV, lending new insight into the vagal regulation of heart rhythm.

    • Ilja M. Nolte
    • , M. Loretto Munoz
    •  & Eco J. C. de Geus
  • Article
    | Open Access

    Type-2 innate lymphoid cells (ILC2) affect adipose tissue metabolism and function. Here the authors show that the ILC2 are present in para-aortic adipose tissue and represent a major source of IL-5 and IL-13 required for mounting atheroprotective immunity, which can be altered by high fat diet.

    • Stephen A. Newland
    • , Sarajo Mohanta
    •  & Ziad Mallat
  • Article
    | Open Access

    Dysfunction of autophagy in plaque macrophages aggravates atherosclerosis. Here the authors show that induction of macrophage autophagy–lysosomal biogenesis either genetically by overexpression of the master transcriptional regulator of this process, TFEB, or pharmacologically with trehalose is atheroprotective.

    • Ismail Sergin
    • , Trent D. Evans
    •  & Babak Razani
  • Article
    | Open Access

    A major cause of transplanted organ failure is graft arteriosclerosis. Qiuet al. show that a key protease of post-translational SUMO modification, SENP1, is crucial for graft arteriosclerosis by regulating the activity of GATA2 transcription factor in the endothelium, and promoting endothelial inflammation and alloimmunity.

    • Cong Qiu
    • , Yuewen Wang
    •  & Luyang Yu
  • Article
    | Open Access

    The human congenital disorder Noonan Syndrome (NS) is caused by germ-line mutations that hyperactivate the RAS/ERK signalling pathway, and can feature pathologic cardiac enlargement. Here, the authors find that a complex cellular and molecular interplay involving a cytokine hierarchy underlies cardiac hypertrophy caused by a NS-associatedRafallele.

    • Jiani C. Yin
    • , Mathew J. Platt
    •  & Benjamin G. Neel
  • Article
    | Open Access

    DNA damage response (DDR) is activated in cardiomyocytes of the failing heart, but the type of DNA damage leading to DDR is unclear. Higoet al. show that in mice heart failure is caused in part by unrepaired DNA single-strand breaks in cardiomyocytes, which activate persistent DDR and trigger an NF-κB-dependent cardiac inflammation.

    • Tomoaki Higo
    • , Atsuhiko T. Naito
    •  & Issei Komuro
  • Article
    | Open Access

    Metoprolol is a selective β1 adrenergic receptor blocker that reduces cardiac infarct size and improves cardiac function. The drug is believed to act on cardiomyocytes; however, here the authors show that metoprolol exerts its beneficial effect on infarcted heart by targeting neutrophils and altering their function and interaction with platelets.

    • Jaime García-Prieto
    • , Rocío Villena-Gutiérrez
    •  & Borja Ibanez
  • Article
    | Open Access

    The molecular pathways regulating the cardioprotective activity of deacetylase sirtuin-1 are unknown. Here, Yanget al. show that histone H3K9 methyltransferase SUV39H and HP1gamma cooperatively methylate H3K9 on the sirtuin-1 promoter and inhibit sirtuin-1 transcription, and show that inhibition of SUV39H in mice is cardioprotective.

    • Guang Yang
    • , Xinyu Weng
    •  & Aijun Sun
  • Article
    | Open Access

    Abatacept is an FDA-approved drug used for treatment of rheumatoid arthritis. Here the authors show that abatacept reduces cardiomyocyte death in a mouse model of heart failure by inhibiting activation and heart infiltration of T cells and macrophages, an effect mediated by IL-10, suggesting a potential therapy for heart failure.

    • Marinos Kallikourdis
    • , Elisa Martini
    •  & Gianluigi Condorelli
  • Article
    | Open Access

    Acute myocardial infarction (AMI) triggers sterile inflammatory reaction mediated by prostaglandin E2 (PGE2). Tang et al. show that the PGE2 via its receptor EP3 promotes cardiac healing after AMI by recruiting reparative Ly6Clowmonocytes/macrophages, which is mediated by TGF-β-driven regulation of CX3CR1 expression and VEGF secretion.

    • Juan Tang
    • , Yujun Shen
    •  & Ying Yu
  • Review Article
    | Open Access

    Vascular endothelium possesses remarkable plasticity in response to cues from its surroundings, leading to great heterogeneity of endothelial cells in different vascular beds. Here the authors explain the molecular basis of endothelial plasticity during embryogenesis and in various diseases.

    • Elisabetta Dejana
    • , Karen K. Hirschi
    •  & Michael Simons
  • Article
    | Open Access

    Catheter ablation is a common therapy for atrial fibrillation but disrupts cardiac cholinergic neurons. Here the authors report that cholinergic neurons innervate heart ventricles and show that their ablation leads to increased susceptibility to ventricular arrhythmias in mouse models and in patients.

    • Christiane Jungen
    • , Katharina Scherschel
    •  & Christian Meyer
  • Article
    | Open Access

    In vivo imaging of inflammation is crucial for detection and monitoring of many pathologies and noninvasive macrophage quantification has been suggested as a possible approach. Here Keliher et al. describe novel polyglucose nanoparticle tracers that are rapidly excreted by the kidney and with high affinity for macrophages in atherosclerotic plaques.

    • Edmund J. Keliher
    • , Yu-Xiang Ye
    •  & Matthias Nahrendorf
  • Article
    | Open Access

    The free fatty acid-mediated inflammatory activities are regulated through TLR4. Here the authors show that palmitic acid binds to MD2, initiating complex formation with TLR4, recruitment of MyD88, and subsequent activation of pro-inflammatory molecules, and that MD2 blockade protects against diet-induced cardiac dysfunction.

    • Yi Wang
    • , Yuanyuan Qian
    •  & Guang Liang
  • Article
    | Open Access

    Lysyl oxidase-like 2 (LOXL2) is an enzyme that promotes scaffolding of extracellular matrix proteins. Here the authors show that LOXL2 is crucial for pressure-overload induced cardiac fibrosis, and that antibody-mediated inhibition or genetic disruption ofLoxl2in mice shows therapeutic potential for treatment of cardiac fibrosis.

    • Jin Yang
    • , Konstantinos Savvatis
    •  & Ching-Pin Chang
  • Article
    | Open Access

    Arteriovenous malformations (AVM) is a hallmark of hereditary haemorrhagic telangiectasia type 2, a disease caused by mutations in BMP receptor ALK1. Ola et al. show that AVM can be caused by blocking BMP9 and BMP10 in mice, leading to increased VEGF and PI3K activity, and that pharmacologic inhibition of PI3K prevents AVM development.

    • Roxana Ola
    • , Alexandre Dubrac
    •  & Anne Eichmann
  • Article
    | Open Access

    Atherosclerosis is caused by low-density lipoprotein (LDL) buildup in the vessel wall, a process thought to be mediated by LDL receptor alone. Here, the authors show that the endothelium can uptake LDL via ALK1, a TGFβ signalling receptor, suggesting new therapies for blocking LDL accumulation in the vessel wall.

    • Jan R. Kraehling
    • , John H. Chidlow
    •  & William C. Sessa
  • Article
    | Open Access

    Signalling pathways that mediate macrophage activation in disease are poorly understood. Here the authors show that inhibition of PARP9 and/or activation of PARP14 may attenuate macrophage-mediated vascular diseases, and also provide new insight into the development of effective therapies for other inflammatory disorders.

    • Hiroshi Iwata
    • , Claudia Goettsch
    •  & Masanori Aikawa
  • Article
    | Open Access

    The stroke volume of the heart increases in response to an increase in the blood volume filling the heart. Here the authors reveal that this coordinated process is mediated in part by oxidative activation of the protein kinase G Iα, which phosphorylates phospholamban to enhance diastolic relaxation in mice.

    • Jenna Scotcher
    • , Oleksandra Prysyazhna
    •  & Philip Eaton
  • Article
    | Open Access

    TREM-1 is a receptor that amplifies acute pro-inflammatory responses in infection. Here the authors show that TREM-1 plays an important role in atherosclerosis, a chronic and non-infectious disease, by critically skewing myelopoiesis towards preferential monocyte differentiation and by contributing to CD36-driven cellular lipid accumulation.

    • Daniel Zysset
    • , Benjamin Weber
    •  & Christoph Mueller
  • Article
    | Open Access

    Bmal1 is a key transcription factor that controls rhythmicity of diverse biological functions. Here, Pan et al. show that Bmal1 deficiency in mice increases lipoprotein secretion and reduces cholesterol excretion to bile, and decipher the molecular mechanisms underlying hyperlipidaemia and atherosclerosis promoted by the lack of Bmal1.

    • Xiaoyue Pan
    • , Christopher A. Bradfield
    •  & M. Mahmood Hussain
  • Article
    | Open Access

    Fever is a defence mechanism against infection, but it may also cause abnormal heart rhythm viaunknown mechanism. Here the authors identify FHF2 protein as a key regulator of myocardial excitability that protects the heart against conduction failure in response to an increase in body temperature.

    • David S. Park
    • , Akshay Shekhar
    •  & Glenn I. Fishman
  • Article
    | Open Access

    Heart responds to increased workload by enlarging cardiomyocytes to preserve function, but in pathologies hypertrophy leads to heart failure. Here the authors show that ANGPTL2 activity in the heart is critical for determining beneficial vs. pathological hypertrophy via its effect on AKT-SERCA2a signaling and myocardial energy.

    • Zhe Tian
    • , Keishi Miyata
    •  & Yuichi Oike
  • Article
    | Open Access

    Platelets express negatively charged phosphatidylserine (PS) on their plasma membrane when propagating coagulation within a developing thrombus. Here the authors show that an adaptor protein 14-3-3 regulates mitochondrial function and PS exposure and thus platelet procoagulant activity, promising a new therapy to reduce thrombosis.

    • Simone M. Schoenwaelder
    • , Roxane Darbousset
    •  & Shaun P. Jackson
  • Article
    | Open Access

    Immune system participates in the development of high blood pressure. Here the authors show that cholinergic-sympathetic pathway mediated by the α7nAChR receptor and the activation of splenic T cells prime immunity during hypertension and that selective splenic denervation protects against the onset of hypertension in mice.

    • Daniela Carnevale
    • , Marialuisa Perrotta
    •  & Giuseppe Lembo
  • Article
    | Open Access

    Congenital heart disease (CHD) is a disorder that occurs in 1% of live births. Here the authors describe a genome-wide allele-specific expression analyses in CHD patients, identifying five new genes involved in CHD and showing that paternally-expressed imprinted genes are monoallelic, while maternally-expressed imprinted genes are biallelic.

    • David M. McKean
    • , Jason Homsy
    •  & J. G. Seidman
  • Article
    | Open Access

    Atherosclerosis progression is linked to inflammatory processes in the blood vessel wall. Here, the authors show that, with the progression of atherosclerosis, the resolution of inflammation is impaired as the result of an imbalance between specialized pro-resolving lipid mediators and leukotrienes.

    • Gabrielle Fredman
    • , Jason Hellmann
    •  & Ira Tabas
  • Article
    | Open Access

    Breaking down the endothelial barrier is a hallmark of systemic inflammatory response syndrome. Here the authors show that palmitoylation, a post-translational modification of proteins, plays a critical role in altering endothelial function during inflammation, and suggest the targeting of palmitoyl acyltransferase DHHC21 as potential disease therapy.

    • Richard S. Beard Jr.
    • , Xiaoyuan Yang
    •  & Sarah Y. Yuan
  • Article
    | Open Access

    The inorganic procoagulant polymer polyphosphate participates in thrombosis via factor XII. Here the authors use recombinant probes that specifically bind or degrade circulating polyphosphate to protect mice in arterial and venous thrombosis models without an increased bleeding risk, the primary complication of all currently used anticoagulants.

    • Linda Labberton
    • , Ellinor Kenne
    •  & Thomas Renné
  • Article
    | Open Access

    Commensal bacteria, the vast majority of which reside in the gut, are involved in development of many diseases, including atherosclerotic vascular disease. Here the authors show that these bacteria remotely increase expression of vascular microRNA-204, which targets Sirt1 in the endothelium to impair endothelial function.

    • Ajit Vikram
    • , Young-Rae Kim
    •  & Kaikobad Irani
  • Article
    | Open Access

    Circulating Ly6Clo monocytes are thought to be derived from Ly6Chi subset. Here the authors show that Notch signalling is activated in Ly6Clocells and is required for their differentiation, and that Notch ligands that initiate this signalling are provided by a subset of endothelial cells.

    • Jaba Gamrekelashvili
    • , Roberto Giagnorio
    •  & Florian P. Limbourg
  • Article
    | Open Access

    Organizers are regions in the embryo that induce cell fate and impart pattern on neighbouring regions. Here, the authors search for new organizers based on a common gene signature, and show that the Anterior Intestinal Portal endoderm induces cardiac identity, specifies ventricle and inhibits atrial character.

    • Claire Anderson
    • , Mohsin A. F. Khan
    •  & Claudio D. Stern
  • Article
    | Open Access

    How p53 is restrained in arterial maturation during embryonic development is unclear. Here, the authors show that β-catenin C-terminal interactions inhibit CREB binding protein-mediated acetylation and activation of p53 in smooth muscle cells, and that this function is essential for artery formation.

    • Dario F. Riascos-Bernal
    • , Prameladevi Chinnasamy
    •  & Nicholas E. S. Sibinga
  • Article
    | Open Access

    5-hydroxymethylation of cysteine (5-hmC) plays a role in epigenetic regulation. Here the authors analyse the hydroxymethylome in embryonic, neonatal, adult and hypertrophic mouse cardiomyocytes and show that the dynamic modulation of hydroxymethylated DNA is important for cardiomyocyte gene expression programming in heart development and failure.

    • Carolina M. Greco
    • , Paolo Kunderfranco
    •  & Gianluigi Condorelli
  • Article
    | Open Access

    Blood supply to the heart is crucial for cardiac function. Here, the authors show that the mitochondrial tryptophanyl-tRNA synthetase, WARS2, drives blood vessel generation in zebrafish and rats and that inhibition of Wars2 diminishes blood vessel growth both within and outside in the heart, suggesting a new target for manipulating angiogenesis.

    • Mao Wang
    • , Patrick Sips
    •  & Stuart A Cook
  • Article
    | Open Access

    The Akt pathway integrates multiple signals, but whether it affects vasculature function is debatable. Here the authors show that Akt pathway shutdown in adult mouse endothelium causes destabilization of vasculature leading to cardiac and retinal dysfunction, due to decreased levels of Jagged1 and impaired Notch signaling.

    • Bethany A. Kerr
    • , Xiaoxia Z. West
    •  & Tatiana V. Byzova
  • Article
    | Open Access

    Understanding coronary vessels development provides basis for regenerative strategies. Here, Soh et al. identify endothelin-1 as a key molecule driving long-term expansion of ISL1+bipotent vascular progenitors derived from human embryonic stem cells, and show that these cells can regenerate coronary vessels in mice.

    • Boon-Seng Soh
    • , Shi-Yan Ng
    •  & Kenneth R. Chien
  • Article
    | Open Access

    In myelinated fibres conduction and adhesion proteins aggregate at discrete foci, but it is unclear if this organization is present in other excitable cells. Using nanoscale visualization and in silico techniques, the authors show that adhesion/excitability nodes exist at the intercalated discs of adult cardiac muscle.

    • Alejandra Leo-Macias
    • , Esperanza Agullo-Pascual
    •  & Mario Delmar
  • Article |

    Mechanical and electrical activity in the heart is propagated through unique cardiomyocyte membrane structures, the intercalated discs (ID). Sharma et al.identify a novel ID protein, Tmem65, that controls Ca2+ signalling and electrical coupling by interacting with and functionally regulating the gap junction protein Cx43.

    • Parveen Sharma
    • , Cynthia Abbasi
    •  & Anthony O. Gramolini
  • Article
    | Open Access

    Adult cardiac progenitor/stem cells (CPSCs) possess valuable potential for heart repair that is limited by the elusiveness of these cells. Here Noseda et al. refine the definition of murine CPSCs producing stem cell antigen 1 (Sca1), mapping the cardiogenic signature and clonogenicity to the subgroup of Sca1+cells expressing PDGFRα.

    • Michela Noseda
    • , Mutsuo Harada
    •  & Michael D. Schneider
  • Article
    | Open Access

    The role of macrophages in hypertension-induced arterial remodeling is poorly understood. Here, Sumida et al. show that high blood pressure drives the alternatively activated macrophages to secrete complement C1q protein, which in turn elicits proliferative β-catenin signalling in the arterial smooth muscle cells.

    • Tomokazu Sumida
    • , Atsuhiko T. Naito
    •  & Issei Komuro