Volume 3 Issue 2, February 2024

Cerebrospinal fluid is now thought to drain through lymphatics instead of veins, but the routes the fluid takes from the subarachnoid space to cervical lymph nodes are unclear. Using advanced imaging, a recent study provides unprecedented anatomical details of lymphatic vessels draining cerebrospinal fluid along the nasopharynx.

Defects in platelet adhesion at sites of injury can lead to excessive bleeding. A study by Gandhi et al. investigates a new bispecific antibody as a possible therapy to prevent bleeding in patients with inherited defects in platelet adhesion.

In coronary artery disease, the transition from an apparently stable state to a life-threatening acute cardiac event is difficult to predict. As such, a recent study applied proteomic and metabolomic approaches to discover new biomarkers that signal imminent myocardial infarction.

In acute myocardial infarction treated with reperfusion, functional preservation of myocardium requires an angiogenic response. A new study shows that CRELD2, an endoplasmic reticulum (ER)-resident protein induced in response to ER stress, acts as an angiocrine factor to limit cardiac dysfunction after ischemia/reperfusion injury in mice.

Regulatory T cells are cardinal players in cardiovascular disease. Research now identifies a noncanonical chemokine signaling pathway that governs the responsiveness and effector functions of these cells in atherosclerosis.

Myocardial infarction causes endoplasmic reticulum (ER) stress, thereby triggering the release of a set of poorly defined growth factors. A study shows that the growth factor CRELD2 is secreted in response to ER stress and is required for preserving heart function after myocardial infarction in mice.

Based on the 19th Global Cardiovascular Clinical Trialists meeting, this Perspective discusses potential sources of evidence that may be used to complement explanatory phase 3 randomized clinical trials and accelerate the development of new cardiovascular medications.

Goerlich et al. review the current knowledge of the cardiovascular complications of the post-COVID condition, including postural orthostatic tachycardia syndrome, myocardial injury, heart failure, myocarditis and arrhythmias, highlighting currently available and potential treatments.

Gustafsson, Lampa et al. used proteomics, metabolomics and clinical factors in a case–cohort study to identify biomarkers of imminent myocardial infarction and devise a prediction model for imminent myocardial infarction, which can be clinically used in the general population.

Shetty et al. report that individuals of African ancestry harboring a high-proportion spliced-in titin truncating variant have a similar increase in the risk of atrial fibrillation, dilated cardiomyopathy and heart failure as individuals of European ancestry.

Selvakumar, Clayton et al. use a porcine model of myocardial infarction and PSC-CM transplantation and identify atrial and pacemaker-like cardiomyocytes as the cause of engraftment arrhythmias and surface marker signatures to distinguish between arrhythmogenic and non-arrhythmogenic cardiomyocytes.

Gandhi, Zivkovic, Østergaard and colleagues describe a bispecific antibody, HMB-001, which could be used for the prophylactic treatment of patients with genetic bleeding disorders, currently treated acutely with recombinant coagulation factor VIIa. HMB-001 can bind and accumulate endogenous FVIIa and localize it to sites of vascular injury by targeting it to the TREM-like transcript-1 receptor selectively expressed on activated platelets.

Wu et al. profile the secretome of cardiac endothelial cells exposed to endoplasmic reticulum (ER) stress during acute myocardial infarction and identify CRELD2 as an angiogenic growth factor supporting infarct repair.

Carramolino et al. show that fibromyocytes and chondromyocytes are selectively depleted, while cap cells are maintained, in regressing mouse plaques.

Döring, van der Vorst, Yan, Neideck et al. present a non-canonical chemokine pathway involving CCL17 signaling through CCR8, which induces CCL3 expression independent of CCR4 and suppresses the functions of atheroprotective T_reg cells.