Cardiology

  • 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
    •  & Ralf H. Adams
  • 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
    •  & Brad E. Zacharia
  • 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
    •  & 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
    •  & 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
    •  & 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
    •  & 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
    •  & Vincent M. Christoffels
  • 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
    •  & Hannele Ruohola-Baker
  • 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
    •  & 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
    •  & 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
    •  & Raj Kishore
  • 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
    •  & 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
    •  & 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
    •  & Guo-Ping Shi
  • 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
    •  & Jonathan M. Hodgson
  • 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
    •  & Enrico Petretto
  • 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
    •  & Renate B. Pilz
  • 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
    •  & Issei Komuro
  • 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
    •  & Euan A. Ashley
  • Article
    | Open Access

    Detailed characterization of cardiac damage following ischemia/reperfusion injury and detection of occurring inflammatory responses is important for the development of new therapeutic concepts. Here the authors present a method for the three-dimensional investigation of acute and chronic cardiac injury responses using light sheet fluorescence microscopy.

    • Simon F. Merz
    • , Sebastian Korste
    •  & Matthias Totzeck
  • Article
    | Open Access

    Mutation of LMNA, encoding Lamin A/C nuclear proteins, cause dilated cardiomyopathy and conduction disorders. Here, the authors show that patient-specific iPSC-derived CMs carrying the K219T LMNA mutation have downregulated Nav1.5 channels due to dynamic cooperation of Lamin A/C and Polycomb repressor complex 2 at the SCN5A promoter.

    • Nicolò Salvarani
    • , Silvia Crasto
    •  & Elisa Di Pasquale
  • Article
    | Open Access

    The development of tissue-engineered vascular grafts heavily relies on the availability of large animal models that allow long-term assessment of graft patency. Here Itoh et al. propose a novel model of immunodeficient pigs that allows long-term accommodation of human cell-derived three-dimensional bioprinted vascular tubes.

    • Manabu Itoh
    • , Yosuke Mukae
    •  & Eiji Kobayashi
  • Article
    | Open Access

    Mitochondrial uncoupling is a treatment strategy for metabolic diseases that reduces the efficiency of mitochondrial oxidative phosphorylation and ATP generation. Here the authors characterize the pharmacokinetic and therapeutic properties of the liver-localized mitochondrial uncoupler OPC-163493, which leads to amelioration of diabetes and hypertension in several rodent disease models.

    • Naohide Kanemoto
    • , Takashi Okamoto
    •  & Seiji Sato
  • Article
    | Open Access

    Implantable medical electronic devices are limited by battery lifetime and inflexibility, but self-powered devices can harvest biomechanical energy. Here the authors demonstrate cardiac pacing and correction of sinus arrhythmia with a symbiotic cardiac pacemaker, which is an implanted self-powered pacing system powered by cardiac motion, in a swine.

    • Han Ouyang
    • , Zhuo Liu
    •  & Zhou Li
  • Article
    | Open Access

    The miR-17-92 cluster has been shown to regulate cardiomyocyte proliferation in vitro and in genetic mutation and overexpression models. Here the authors show that the cluster member miR-19a/19b regulates cardiomyocyte proliferation in vivo, and that delivery of miR-19a/19b to the heart leads to both short-term and long-term protective responses to myocardial infarction.

    • Feng Gao
    • , Masaharu Kataoka
    •  & Da-Zhi Wang
  • Article
    | Open Access

    Atrial fibrillation (AF) is accompanied by a detrimental loss of functional cardiomyocytes. Here, Zhang et al. show that AF-induced cardiomyocyte dysfunction is a consequence of DNA damage-mediated PARP1 activation, which leads to depletion of NAD+ and further oxidative stress and DNA damage, and identify PARP1 inhibition as a potential therapeutic strategy in the treatment of AF.

    • Deli Zhang
    • , Xu Hu
    •  & Bianca J. J. M. Brundel
  • Article
    | Open Access

    Studying adrenergic signalling in the heart requires perfusion with receptor agonists, which lacks cell specificity and spatiotemporal control. Here the authors use the light sensitive G-coupled receptor JellyOp to optogenetically control Gs-signaling in cardiomyocytes and intact hearts with high spatiotemporal precision.

    • Philipp Makowka
    • , Tobias Bruegmann
    •  & Philipp Sasse
  • Article
    | Open Access

    Somatic heterozygous TET2 loss drives clonal hematopoiesis, which is linked to malignant cell degeneration and potentially cardiovascular disease. Here, the authors investigate the molecular impact of a germline TET2 mutation in a lymphoma family, finding elevated blood DNA methylation levels and no predisposition to atherosclerosis

    • Eevi Kaasinen
    • , Outi Kuismin
    •  & Lauri A. Aaltonen
  • Article
    | Open Access

    Vascular calcification is a hallmark of end stage renal disease. Here, Cheng et al. show that poly(ADP-ribose) polymerase (PARP) activity is increased in calcified arteries in patients and uremic rats, and that PARP1 promotes vascular calcification by suppressing miR-204 expression via IL-6/STAT3 signaling, thus relieving repression of the osteogenic regulator Runx2.

    • Cheng Wang
    • , Wenjing Xu
    •  & Kai Huang
  • Article
    | Open Access

    During myocardial infarction, microRNAs (myo-miRs) are released into the circulation. Here Cheng et al. show that myo-miRs carried in exosomes are transferred to the bone marrow (BM), downregulate expression of CXCR4 in mononuclear cells, and increase the number of circulating BM progenitor cells, thus orchestrating a systemic response to myocardial injury.

    • Min Cheng
    • , Junjie Yang
    •  & Gangjian Qin
  • Article
    | Open Access

    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
    •  & Andreas Dendorfer
  • Article
    | Open Access

    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
    •  & Jeffery D. Molkentin
  • Article
    | Open Access

    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
    •  & Cecilia M. Lindgren
  • Article
    | Open Access

    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
    •  & Zhi-Ping Liu
  • Article
    | Open Access

    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
    •  & Norihiro Kato
  • Article
    | Open Access

    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
    •  & Bhama Ramkhelawon
  • Article
    | Open Access

    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
    •  & Miguel R. Campanero
  • Article
    | Open Access

    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
    •  & Dietmar Schmitz
  • Article
    | Open Access

    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