Reviews & Analysis

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  • Targeting the Notch ligand DLL4 in adult liver vessels induced transcriptional states associated with endothelial cell (EC) proliferation and sprouting. However, genetic and pharmacological inhibition of these angiogenic cell states did not prevent an abnormal vasculature and pathology in the liver, suggesting that transcriptional states do not always inform on the vascular phenotype and related pathophysiology.

    Research Briefing
  • Flam and Arany review the current knowledge of how the signaling intermediate metabolites affect the heart in health and disease.

    • Emily Flam
    • Zolt Arany
    Review Article
  • Our study demonstrates that statins improve endothelial function and vascular health by inhibiting the epigenetic activation of the YAP–SOX9 signaling axis and subsequently preventing endothelial-to-mesenchymal transition in conditions associated with an increased risk of cardiovascular disease, such as type 2 diabetes.

    Research Briefing
  • Statins exert cardiovascular protective effects that are independent of cholesterol lowering. Using endothelial cells derived from induced pluripotent stem cells, Liu et al. show that statins can improve endothelial dysfunction by inhibiting endothelial–mesenchymal transition via epigenetic regulation of the GGTase–RhoA–YAP1–SOX9 signaling pathway.

    • Seongho Bae
    • Cholomi Jung
    • Young-sup Yoon
    News & Views
  • Preserving hemostasis while preventing pathological thrombosis has been a central goal in drug development. A new way to restore hemostasis is suggested by the finding that glycoprotein V is cleaved by thrombin on activated platelets, negatively regulating clotting at sites of vascular injury.

    • Elizabeth A. Knauss
    • Marvin T. Nieman
    News & Views
  • Lopaschuk and Dyck review the bioenergetic and signaling effects of ketones on the cardiovascular system and discuss the potential application of ketones for treating cardiovascular diseases.

    • Gary D. Lopaschuk
    • Jason R. B. Dyck
    Review Article
  • Smith and Edelman discuss recent advances in cardiovascular and blood nanomedicine and highlight key clinical applications and opportunities.

    • Bryan Ronain Smith
    • Elazer R. Edelman
    Review Article
  • Conlon and Arnold discuss the sex differences in cardiac physiology and pathology, the sex-chromosome pathways underlying such differences, and future studies that are needed to assess how cardiac sex differences are maintained and propagated.

    • Frank L. Conlon
    • Arthur P. Arnold
    Review Article
  • Calcium sparks are the elementary detectable units of calcium release through ryanodine receptors (RyRs). Hou et al. correlate Ca2+ sparks with RyR cluster configurations and provide insights into the dynamics of Ca2+ release in live cardiomyocytes at baseline and in pathological conditions.

    • Laetitia Pereira
    • Almudena Val-Blasco
    • Ana M. Gómez
    News & Views
  • We report an intronic variant of the endothelial angiopoietin receptor TIE2 that is associated with increased gene expression and decreased risk of coronary artery disease. Genetic deletion of Tie2 in hypercholesterolemic mice shows that the Tie2 receptor protects from atherosclerosis by controlling inflammation in the arterial wall.

    Research Briefing
  • Specialized endothelial cells within certain embryonic blood vessels can generate hematopoietic cells. A recent study reveals blood-forming capacity also within embryonic lymphatic endothelium, which is suppressed during normal development by the lymphatic endothelial fate-determining transcription factor PROX1.

    • Taija Mäkinen
    News & Views
  • Variants in the alpha kinase 3 (ALPK3) gene cause cardiomyopathy, but we have little understanding of the mechanisms at play. We demonstrate that ALPK3 forms a critical signaling node that links contractile proteins to protein quality control machinery. These findings may open new therapeutic approaches to treat cardiomyopathies.

    Research Briefing
  • The mechanisms that link altered metabolism and heart failure remain unclear. A new study defines the role of the lysine demethylase KDM8 in preventing the initiation of dilated cardiomyopathy through epigenetic control of homeostatic cardiac metabolism.

    • Sayan Bakshi
    • Adam R. Wende
    News & Views
  • We report a new non-invasive approach to track neutrophils in both mice and humans by directing multimodal fluorine-loaded nanotracers equipped with specific binding peptides to neutrophil surface markers to enable background-free readout by in vivo 19F MRI.

    Research Briefing
  • Tissue infiltration of neutrophils is a key event of sterile and pathogen-induced inflammation; however, there is at present no non-invasive tool to visualize neutrophil dynamics in the body. Bouvain et al. develop a neutrophil-specific tracer that enables longitudinal imaging of neutrophil flux across the whole body.

    • Oliver Soehnlein
    News & Views
  • Clonal hematopoiesis of indeterminate potential (CHIP) is a blood disorder that can increase the risk of cardiovascular disease. A new study reveals that CHIP driven by somatic mutations in DNA damage repair genes increases the risk of CVD in humans, and provides mechanistic insights in murine models.

    • Prabhakara R. Nagareddy
    • Andrew J. Murphy
    News & Views
  • Using cap analysis of gene expression, we have constructed a map of the genome regulatory network (promoters and enhancers) in healthy and failing human hearts. Analysis of this map demonstrates differential transcriptional regulation in cardiac chambers, disease states, and ischemic and non-ischemic cardiomyopathies. This information could lead to tailored therapies.

    Research Briefing