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  • Changes in gene regulatory networks leading to species-specific variations in cardiac structure and function remain to be fully investigated. A new study presents a repertoire of human-gained (absent in mice) cis-regulatory elements, some of which appear to be involved in the acquisition of human-specific cardiac features.

    • Mirana Ramialison
    News & Views
  • Sex–age disparities in disease risk have been a neglected topic in cardiometabolic disease research. Zhernakova et al. demonstrate that risk factors and metabolic predictors covary with both sex and age: that is, men and women are different, and these differences are not static but change with age.

    • Jack J. Miller
    • Lisa C. Heather
    News & Views
  • Recent developments in high-throughput, in-depth sequencing platforms are providing opportunities to improve our understanding of biology and disease. Here, Kuppe et al. use a combinatorial approach to relate transcriptional changes to translational and functional implications for the heart in response to myocardial infarction.

    • Martijn Wehrens
    • Louk T. Timmer
    • Eva van Rooij
    News & Views
  • A landscape view of metabolic remodeling in end-stage human failing hearts generated by multiomics analysis confirms main changes in cardiac energy metabolism and challenges several widely held mechanisms derived from animal models. Further validation in non-end-stage heart failure and metabolic flux analysis will be necessary to move the field forward.

    • Akira Yoshii
    • Rong Tian
    News & Views
  • Collateral arteries may act as natural bypasses that reduce hypoperfusion after a coronary blockage. 3D imaging of neonatal and adult mouse hearts, plus human fetal and diseased adult hearts, is now used to computationally predict flow within the heart, and understand the cardioprotective role of collateral arteries in vivo.

    • David Mayerich
    • Joshua D. Wythe
    News & Views
  • The replacement of damaged cardiomyocytes by extracellular matrix-producing fibroblasts underpins adverse remodeling in the failing heart. New research finds that MHC class II-dependent fibroblast–CD4+ T cell interactions in the myocardium lead to fibroblast activation and exacerbate fibrotic remodeling of the myocardium.

    • Christian Perez-Shibayama
    • Cristina Gil-Cruz
    • Burkhard Ludewig
    News & Views
  • Thrombocytopenia is common in severe sepsis and is associated with an increased risk of mortality. A new study shows that platelet pyroptosis initiated during infection promotes a feedforward loop of neutrophil-mediated inflammation that worsens outcomes during sepsis.

    • Luke Brown
    • Bryan G. Yipp
    News & Views
  • Transiently inducing proliferation of adult cardiomyocytes is a long-sought goal in the cardiac regeneration field. A new study shows that genetic deletion of calcineurin B1 and treatment with FK506 (tacrolimus, an FDA-approved inhibitor of calcineurin) induce cardiomyocyte proliferation in adult mice.

    • Hirofumi Watanabe
    • Henry M. Sucov
    News & Views
  • Viral infections and cardiovascular disease (CVD) share a two-way connection: viral infection can raise CVD risk, and people with CVD are more prone to severe viral infection. Zhao et al. now detail a molecular mechanism whereby macrophages from patients with CVD inhibit antiviral T cell responses via immune checkpoint activation.

    • Siroon Bekkering
    • David Burgner
    News & Views
  • A mouse model of spontaneous arrhythmia in awake mice enables researchers to study how immune cells contribute to this process. The authors find opposing effects of the immune compartment, with neutrophils favoring arrhythmias by increasing oxidative stress and macrophages protecting against it via their phagocytic activity.

    • José Ángel Nicolás-Ávila
    • Andrés Hidalgo
    News & Views
  • The stretch-activated ion channel Piezo1 senses biomechanical stress and provides calcium for transcriptional activation and cardiac growth. In turn, the high amplitude of calcium determines specific signaling through the CaMKII–HDAC–MEF2 pathway as opposed to the calcineurin–NFAT pathway.

    • Johannes Backs
    News & Views
  • A prospective observational case-report study now shows that thalidomide can be a well-tolerated, efficacious treatment for complications such as pain, bleeding and ulceration from extracranial arteriovenous malformation.

    • Joyce M. C. Teng
    • Dawn H. Siegel
    News & Views
  • Clonal hematopoiesis is a risk factor for hematological cancers, cardiovascular diseases and death. Two papers now use new experimental and mathematical tools to quantify changes in the clonal composition of human blood over time, and the results have implications for the risk of cardiovascular diseases.

    • Siddhartha Jaiswal
    • Alexander G. Bick
    News & Views
  • Rupture or dissection of the aorta is often fatal. Tcheandjieu and colleagues now identify key pathways underlying aortic dilatation, a common prelude to acute aortic events, and assess the utility of a polygenic risk score to identify those at highest risk of aortic death in whom prophylactic surgical repair may be beneficial.

    • Corry Gellatly
    • Matthew J. Bown
    News & Views
  • Blood vessels are thought to form either by de novo vasculogenesis or by angiogenesis from pre-existing blood vessels. Research now finds that anal fin blood vessels form by endothelial transdifferentiation from lymphatic vessels.

    • Michael Jeltsch
    • Kari Alitalo
    News & Views
  • Dysregulation of voltage-gated cardiac Na channels can be arrhythmogenic. A new study shows that splice variants of fibroblast growth factor homologous factors (FHFs) can either promote or suppress arrhythmogenic late Na current, and the peptide inhibitor FixR could represent a therapeutic strategy to treat cardiac arrhythmias.

    • Bence Hegyi
    • Donald M. Bers
    News & Views
  • Blood vascular leakage in conjunction with stroke causes edema and a worsened outcome. Through augmented and selective tyrosine phosphatase activity, endothelial junctions can be sealed, resulting in reduced stroke volume and improved survival.

    • Mark Richards
    • Lena Claesson-Welsh
    News & Views
  • Apelin is a multifunctional peptide that stimulates angiogenesis in a VEGF-A-dependent manner. A study now shows that apelin produced by intestinal endothelium drives VEGF-A-independent angiogenesis in intestinal crypts and is needed for the homeostasis of crypt-resident stem or progenitor cells.

    • Gou Young Koh
    News & Views
  • Loss of transcription factor SMAD3 changes the smooth muscle cell (SMC) to a unique remodeling SMC phenotype and points to a potential role for SMAD3 in the inhibition of macrophage recruitment and outward remodeling of the aortic wall.

    • Marie Jose Goumans
    • Paul H. A. Quax
    News & Views
  • Genome-wide association studies of magnetic resonance imaging (MRI) of diastolic heart function shed light on the underlying molecular mechanisms and support a causal role of diastolic function for the development of heart failure.

    • J. Gustav Smith
    • Olof Gidlöf
    News & Views