Volume 1 Issue 12, December 2022

Sleep modulates cardiovascular health, and recent studies have begun to uncover underlying mechanistic links. An integrated translational approach that combines animal models and human trials will enrich scientific discovery, improve therapy, and help to alleviate the global burden of insufficient sleep and cardiovascular disease.

In the COVID-19 aftermath, academia experiences an unprecedented drought of postdoctoral researchers. The new generation of scientists refuses to face the low odds of starting their own labs in a competitive arena that does not align with their work–life balance needs. We discuss the possible reasons and potential measures needed to sustain talented and passionate early career researchers in academia.

Although cardiac arrhythmias have been observed and described during and after SARS-CoV-2 infection, rigorous studies designed to untangle the complex relationship between this proinflammatory illness and arrhythmogenesis are limited. Despite a pervasive opinion to the contrary, there is presently no definitive data to establish a causal, viral-specific association between COVID-19 and incident arrhythmia.

Cytotoxic T cells react to cardiac peptides in patients with cancer that receive immunotherapy, resulting in myocarditis. Identifying the targets for T cells in patients who are immunosuppressed will enable a better understanding of individual risk before treatment is initiated

A new study shows that brain-resident parenchymal border macrophages (PBMs) maintain perivascular extracellular matrix composition by the release of matrix metalloproteinases. Depletion of PBMs suppressed glymphatic fluid transport, underscoring their responsibility for perivascular space homeostasis and brain protein clearance.

Regulation of endothelial barrier function is critical to physiological function of the vasculature, which must dynamically change in many physiologic and pathologic settings. A new study emphasizes the complex relationship between VE-cadherin phosphorylation and vascular leak and the critical role of the tyrosine kinase Yes in this process.

Postural orthostatic tachycardia syndrome (POTS) can follow COVID-19 as part of the post-acute sequelae of SARS-CoV-2 infection, but it can also develop after COVID-19 vaccination, although at a lower frequency.

Increasing evidence suggests that IGFBP7 may be an accurate biomarker for heart failure. A new study shows that beyond its diagnostic value, IGFBP7 may drive the detrimental effects of pressure overload in mice by a mechanism that, at least in part, involves the regulation of senescence by an IGF-1R–IR–FOXO3a signaling cascade.

The contribution of platelets to atherothrombosis is well established. Accumulating genome-wide association studies have revealed several variants of genes encoding molecules along the nitric oxide (NO)–soluble guanylyl cyclase (sGC)–cyclic guanosine-3′,5′-monophosphate (cGMP) pathway that are associated with increased risk of coronary artery disease; however, the cell types and functional impact of these risk variants remain poorly understood. Mauersberger et al. now demonstrate that platelet-specific knockout of a transcript encoding sGC increased atherosclerosis, whereas pharmacological stimulators of sGC reduced lesions via a paracrine effect of angiopoietin-1 on endothelial cell–leukocyte interactions.

Preemptive identification of unstable, ‘vulnerable’ atherosclerotic plaques is important for predicting the risk of thrombotic events. A new study shows that unbiased classification of human atherosclerotic plaques on the basis of transcriptomic features identifies subgroups with distinct biology and clinical presentation.

The epicardium has an active role in the formation of fetal and neonatal mammalian hearts, which retain the ability to regenerate. A single-cell comparison of human fetal and adult epicardial cells defines the transcriptomic programs that are specific to the fetal epicardium that could be harnessed to repair the injured adult heart.

Postural orthostatic tachycardia syndrome (POTS) has been observed following SARS-CoV-2 infection. In this study, we observed occurences of POTS following COVID-19 vaccination, albeit at a lower rate than following COVID-19 infection.

Clustering the atherosclerotic plaques of patients based on gene expression unearths novel and clinically relevant heterogeneity beyond the established dogma of ‘stable’ and ‘unstable’ plaques.

Endothelial cell–cell contacts in blood vessels constitute a barrier to the flux of molecules and cells from blood to tissues. We identified the tyrosine-protein kinase Yes as the principal regulator of collective endothelial cell migration and vascular barrier dynamics, a finding that opens avenues for future therapeutic development.

The mechanisms of adrenergic stimulation of cardiac voltage-gated calcium (Ca_V) channels have remained elusive. Using proximity proteomics and genetically altered mice, we show that phosphorylation of the Ca_V channel inhibitor Rad is essential for regulation, by the sympathetic nervous system, of calcium influx, and for augmentation of cardiac contractility.

Mokry et al. performed bulk RNA sequencing of 654 advanced human carotid plaques from the Athero-Express biobank and 162 coronary samples, and they show that unsupervised clustering defines plaque types corresponding to different cell compositions and clinical presentations. Circulating biomarkers can be potentially used to mark the different transcriptomic-defined plaque phenotypes.

Jin and coauthors show that Yes-mediated tyrosine phosphorylation is critical for VE-cadherin’s constitutive internalization and junctional pliability in endothelial cells, but it is not required for the induction of vascular leakage.

Mauersberger and colleagues show that loss of function of soluble guanylyl cyclase (sGC) in platelets increases plaque burden in atherosclerosis-prone Ldlr^−/− mice by increasing leukocyte adhesion to atherosclerotic plaques. While mouse platelets lacking sGC and human platelets from carriers of GUCY1A1 risk alleles showed reduced secretion of angiopoietin-1, pharmacological sGC stimulation increased platelet angiopoietin-1 release in vitro and reduced leukocyte recruitment and atherosclerotic plaque formation in vivo, suggesting sGC as a potential therapeutic target for the treatment and prevention of atherosclerosis.

Through analysis of the electronic medical records of 284,592 vaccinated patients, using a sequence–symmetry analysis, Kwan et al. show that the risk of postural orthostatic tachycardia syndrome (POTS) is increased after COVID-19 vaccination compared to a 90-day control period before exposure—although 5.35 times lower than the risk of POTS occurrence after SARS-CoV-2 infection.

Zhang et al. show increased blood concentration of IGFBP7 in patients and a mouse model with heart failure (HF). IGFBP7 promotes cardiac senescence by stimulating IGF-1R/IRS/AKT-dependent suppression of FOXO3a, and Igfbp7 deficiency or inhibition attenuates cardiac dysfunction in a pressure overload mouse HF model, suggesting that therapeutic targeting of IGFBP7 might be promising for the treatment of HF.

Knight-Schrijver et al. use single-cell and single-nuclei RNA sequencing to profile the human fetal and adult epicardium in homeostatic conditions. The analysis shows fetal-specific epicardial gene programs that could support heart regeneration.