Cardiology articles within Nature Communications

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  • Article
    | Open Access

    Coronary artery calcium is an accurate predictor of cardiovascular events but this information is not routinely quantified. Here the authors show a robust and time-efficient deep learning system to automatically quantify coronary calcium on CT scans and predict cardiovascular events in a large, multicentre study.

    • Roman Zeleznik
    • , Borek Foldyna
    •  & Hugo J. W. L. Aerts

  • Article
    | Open Access

    ZEB2 transcription factor is increased in a subset of cardiomyocytes during stress to induce cardioprotective effects after injury. Here the authors show that therapeutic delivery of ZEB2 prevents cardiac dysfunction after ischemic damage and promotes the activation of pro-angiogenic signals.

    • Monika M. Gladka
    • , Arwa Kohela
    •  & Eva van Rooij

  • Article
    | Open Access

    Muscle cells express an adhesion molecule called metavinculin, which has been associated with cardiomyopathies. Here, the authors employed molecular tension sensors to reveal that metavinculin expression modulates cell adhesion mechanics and they develop a mouse model to demonstrate that the presence of metavinculin is not as critical for heart muscle function as previously thought.

    • Verena Kanoldt
    • , Carleen Kluger
    •  & Carsten Grashoff

  • Article
    | Open Access

    Blood eosinophil (EOS) counts may serve as risk factors for human coronary heart diseases. Here the authors show that increased circulating and myocardial EOS after myocardial infarction play a cardioprotective role by reducing cardiomyocyte death, cardiac fibroblast activation and fibrosis, and endothelium activation-mediated inflammatory cell accumulation.

    • Jing Liu
    • , Chongzhe Yang
    •  & Guo-Ping Shi

  • Article
    | Open Access

    The involvement of cAMP-dependent regulation of HCN4 in the chronotropic heart rate response is a matter of debate. Here the authors use a knockin mouse model expressing cAMP-insensitive HCN4 channels to discover an inhibitory nonfiring cell pool in the sinoatrial node and a tonic and mutual interaction between firing and nonfiring pacemaker cells that is controlled by cAMP-dependent regulation of HCN4, with implications in chronotropic heart rate responses.

    • Stefanie Fenske
    • , Konstantin Hennis
    •  & Christian Wahl-Schott

  • Article
    | Open Access

    Cardiac dysfunction is a major complication that precedes death after scorpion envenomation. Here, authors show that heart failure and mortality are caused by excessive acetylcholine release, which requires IL-1R-dependent PGE2 production. Dexamethasone treatment effectively inhibits cardiac dysfunction and mortality.

    • Mouzarllem B. Reis
    • , Fernanda L. Rodrigues
    •  & Lúcia H. Faccioli

  • Article
    | Open Access

    Here, the authors apply genetic fate mapping and temporal clonal analysis to study progenitor recruitment and network morphogenesis of murine cardiac Purkinje fibers. Additionally, they characterize how transcription factor dosage regulates cell fate divergence during distinct phases of this process.

    • Caroline Choquet
    • , Robert G. Kelly
    •  & Lucile Miquerol

  • Article
    | Open Access

    Three-dimensional imaging of the fetal heart and quantification of blood flow in the surrounding vessels is very challenging because the heart is small and the fetus is free to move in the womb. Here, the authors demonstrate motion-corrected 4D flow MRI of the whole fetal heart and major vessels.

    • Thomas A. Roberts
    • , Joshua F. P. van Amerom
    •  & Joseph V. Hajnal

  • Article
    | Open Access

    Cardiotoxic adverse events associated with kinase inhibitors are a growing concern in clinical oncology. Here the authors use cellular transcriptomic responses of human cardiomyocytes treated with protein kinase inhibitors and the associated drug structural signatures to determine an integrated predictive signature of cardiotoxicity.

    • J. G. Coen van Hasselt
    • , Rayees Rahman
    •  & Ravi Iyengar

  • Article
    | Open Access

    The pathogenic mechanisms of cardiorenal syndrome type 4 (CRS4) remain unclear. Here, the authors identify IRF1-PGC1α axis-mediated myocardial energy metabolism remodeling as a contributor to CRS4 pathogenesis, thus providing potential new targets for reducing cardiovascular events in CKD patients.

    • Yinghui Huang
    • , Shaobo Wang
    •  & Jinghong Zhao

  • Article
    | Open Access

    Prediabetes has been associated with diabetes complications, but these relationships may be confounded. Here the authors show, using genetic data in causal inference analyses, that prediabetes raises risk of coronary heart disease, but not other diabetes complications.

    • Pascal M. Mutie
    • , Hugo Pomares-Millan
    •  & Paul W. Franks

  • Article
    | Open Access

    Arterial macrophages develop from either yolk sac or bone marrow progenitors. Here, the author show that ageing-induced reduction of arterial macrophages is not replenished by bone marrow-derived cells, but under inflammatory conditions circulating monocytes are recruited to maintain homeostasis, while arterial macrophages of yolk sac origin carry out tissue repair.

    • Tobias Weinberger
    • , Dena Esfandyari
    •  & Christian Schulz

  • Article
    | Open Access

    Little is known about how cardiac metabolism remodels following cardiac injury. Here, the authors show that mitochondrial CaMKII plays an important role in remodeling cardiac metabolism after injury and that replacement of mitochondrial creatine kinase improves energetics and protects against adverse remodeling.

    • Elizabeth D. Luczak
    • , Yuejin Wu
    •  & Mark E. Anderson

  • Article
    | Open Access

    The pathophysiological role of dopamine D1 receptor (D1R) in chronic heart failure remains elusive. Here the authors show that D1R-expressing cardiomyocytes appear in chronic heart failure and play a pivotal role in triggering lethal ventricular arrhythmias.

    • Toshihiro Yamaguchi
    • , Tomokazu S. Sumida
    •  & Issei Komuro

  • Article
    | Open Access

    Na+ has been suggested to accumulate in tissues, particularly skin, in a hypertonic manner and to exert local pathogenic effects. Here, we reappraise this phenomenon which is systemic in nature and reflects isotonic changes in the relative extracellular volume in tissues, e.g. subclinical oedema; as such, it occurs in human hypertension and aging.

    • Giacomo Rossitto
    • , Sheon Mary
    •  & Christian Delles

  • Article
    | Open Access

    Genetic variation predisposes to disease via monogenic and polygenic risk variants. Here, the authors assess the interplay between these types of variation on disease penetrance in 80,928 individuals. In carriers of monogenic variants, they show that disease risk is a gradient influenced by polygenic background.

    • Akl C. Fahed
    • , Minxian Wang
    •  & Amit V. Khera

  • Article
    | Open Access

    Despite recent progress to advance cardiac cell-based therapy for patients, heart failure mortality rivals most cancers. Here, the authors describe an approach to control and pattern 3 distinct human cardiac cell populations to promote superior repair and regeneration after myocardial infarction.

    • Megan M. Monsanto
    • , Bingyan J. Wang
    •  & Mark A. Sussman

  • Article
    | Open Access

    Supercentenarians are approaching the current longevity limit by avoiding or surviving major illness, thus identifying biomarkers for exceptional survival might provide insights into the protection against disease of aging. Here, the authors show low NT-proBNP and high albumin in plasma are the biological correlates of survival to the highest ages.

    • Takumi Hirata
    • , Yasumichi Arai
    •  & Nobuyoshi Hirose

  • Article
    | Open Access

    Omecamtiv mecarbil is a small molecule effector under clinical trial for the treatment of systolic heart failure. Here the authors define the molecular mechanisms of its inotropic action and find it can increase the efficiency of contraction in muscle fibres when the orthophosphate concentration rises with the beat frequency.

    • Serena Governali
    • , Marco Caremani
    •  & Marco Linari

  • Article
    | Open Access

    Restoration of coronary blood flow after a heart attack may lead to reperfusion injury and pathologic iron deposition. Here, the authors perform magnetic susceptibility imaging showing its association with iron in a large animal model of myocardial infarction during wound healing, and showing feasibility in acute myocardial infarction patients undergoing percutaneous coronary intervention.

    • Brianna F. Moon
    • , Srikant Kamesh Iyer
    •  & Walter R. Witschey

  • Article
    | Open Access

    Extravasated erythrocytes in cerebrospinal fluid (CSF) contribute to the pathogenesis of subarachnoid haemorrhage (SAH). Here, the authors show that meningeal lymphatics drain extravasated erythorcytes and that blockage of this drainage aggravates SAH severity.

    • Jinman Chen
    • , Linmei Wang
    •  & Yongjun Wang

  • Article
    | Open Access

    Study of human heart failure is limited by access to human tissue. Here, the authors apply multi-omic screening in human ischaemic and dilated myocardial tissue and matched controls to determine molecular changes common and unique to each aetiology and to reveal differences between male and female hearts.

    • Mengbo Li
    • , Benjamin L. Parker
    •  & John F. O’Sullivan

  • Article
    | Open Access

    On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.

    • Ioanna Ntalla
    • , Lu-Chen Weng
    •  & Patricia B. Munroe

  • Article
    | Open Access

    Structural changes to the left ventricle are characteristic of dilated cardiomyopathy (DCM), a disease for which many rare genetic variants are known. Here, Pirruccello et al. report GWAS of seven cardiac MRI measurements in the left ventricle and describe shared loci and polygenic association with DCM.

    • James P. Pirruccello
    • , Alexander Bick
    •  & Krishna G. Aragam

  • Article
    | Open Access

    Arterial degeneration, closely associated with cardiovascular diseases, is driven by aging-related vascular cell-specific transcriptomics changes. This study provides a single-cell transcriptomic atlas for senile aortic and coronary arteries and underscores FOXO3A-based the transcriptional network in vasoprotection during aging.

    • Weiqi Zhang
    • , Shu Zhang
    •  & Jing Qu

  • Article
    | Open Access

    SGLT2 inhibitors, a class of type 2 diabetes medication, reduce cardiovascular events in patients beyond expectation from blood sugar control. Here the authors report a randomized controlled trial showing that SGLT2 inhibitors reduce inflammasome activation in peripheral macrophages, which may contribute to the cardiovascular protection.

    • So Ra Kim
    • , Sang-Guk Lee
    •  & Yong-ho Lee

  • Article
    | Open Access

    Senolytics have the potential to extend healthspan by selectively killing senescent cells (SCs), but senolytics that target Bcl-xl may cause platelet toxicity. Here, the authors generated a Bcl-xl proteolysis-targeting chimera (PROTAC) senolytic, which effectively clears SCs and rejuvenates tissue stem and progenitor cells in naturally aged mice without causing severe thrombocytopenia.

    • Yonghan He
    • , Xuan Zhang
    •  & Daohong Zhou

  • Article
    | Open Access

    The molecular mechanisms that drive irreversible acute liver failure remain poorly characterized. Here, the authors show that the recently discovered platelet receptor CLEC-2 (C-type lectin-like receptor) perpetuates and worsens liver damage during acute liver injury by blocking restorative neutrophil driven inflammation.

    • Abhishek Chauhan
    • , Lozan Sheriff
    •  & Patricia F. Lalor

  • Article
    | Open Access

    Epidemiological studies have shown an association between sedentary behaviours and cardiovascular disease risk. Here, van de Vegte et al. perform GWAS for self-reported sedentary behaviours (TV watching, computer use, driving) and Mendelian randomization analyses to explore potential causal relationships with coronary artery disease.

    • Yordi J. van de Vegte
    • , M. Abdullah Said
    •  & Niek Verweij

  • Article
    | Open Access

    The role of automatic electrocardiogram (ECG) analysis in clinical practice is limited by the accuracy of existing models. In that context, the authors present a Deep Neural Network (DNN) that recognizes different abnormalities in ECG recordings which matches or outperform cardiology and emergency resident medical doctors.

    • Antônio H. Ribeiro
    • , Manoel Horta Ribeiro
    •  & Antonio Luiz P. Ribeiro

  • Article
    | Open Access

    Pulmonary arterial hypertension (PAH) is a heterogeneous disease, causing severe breathing problems and cardiac morbidity. Here, the authors study chromatin marks in pulmonary arterial endothelial cells from PAH patients and controls and find changes in transcription factor and enhancer activity that suggest an aberrant response to signalling in PAH.

    • Armando Reyes-Palomares
    • , Mingxia Gu
    •  & Judith B. Zaugg

  • Article
    | Open Access

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are essential for rhythmic activity in the heart and brain. Here authors reverse the voltage dependence of HCN channels by mutating only two residues located at the interface between the voltage sensor and the pore domain.

    • Rosamary Ramentol
    • , Marta E. Perez
    •  & H. Peter Larsson

  • Article
    | Open Access

    Reperfusion injury following myocardial ischemia is aggravated by inflammation and platelet–neutrophil complex formation. Here the authors show that semaphorin 7A binds to platelet GPIb, enhancing platelet–neutrophil interaction and increasing post-ischemic myocardial tissue injury, and that blockage of semaphorin 7A is protective.

    • David Köhler
    • , Tiago Granja
    •  & Peter Rosenberger

  • Article
    | Open Access

    Pulmonary arterial hypertension is a severe lung disease characterised by progressive vascular remodelling. Here, the authors show that reduced signalling of flow-activated transcription factor KLF2 is a common feature of human PAH and that KLF2-regulated exosomal miRNAs have a therapeutic effect.

    • Hebah A. Sindi
    • , Giusy Russomanno
    •  & Beata Wojciak-Stothard

  • Article
    | Open Access

    Cardiovascular calcification is a serious pathology for which effective pharmacological treatments are lacking. Here the authors show that an optimized oligo(ethylene glycol) derivative of inositol phosphate interferes with calcium phosphate crystallization and inhibits soft tissue calcification in vivo following subcutaneous injection.

    • Antonia E. Schantl
    • , Anja Verhulst
    •  & Jean-Christophe Leroux

  • Article
    | Open Access

    miR-132 was shown to drive pathological cardiac remodeling, a hallmark of heart failure. Here, the authors show that an antisense inhibitor of miR-132 has favourable pharmacokinetics, safety-tolerability and preclinical efficacy in mouse and porcine models of heart failure.

    • Ariana Foinquinos
    • , Sandor Batkai
    •  & Thomas Thum

  • Article
    | Open Access

    Macrophages mediate the fibrotic response after a heart attack by extracellular matrix turnover and cardiac fibroblasts activation. Here the authors identify an evolutionarily-conserved function of macrophages that contributes directly to the forming post-injury scar through cell-autonomous deposition of collagen.

    • Filipa C. Simões
    • , Thomas J. Cahill
    •  & Paul R. Riley

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