CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 ER Maastricht, the Netherlands; Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal. Electronic address:
Published: June 2023
AI Article Synopsis
Article Abstract
While it is experimentally supported that impaired myocardial vascularization contributes to a mismatch between myocardial oxygen demand and supply, a mechanistic basis for disruption of coordinated tissue growth and angiogenesis in heart failure remains poorly understood. Silencing strategies that impair microRNA biogenesis have firmly implicated microRNAs in the regulation of angiogenesis, and individual microRNAs prove to be crucial in developmental or tumor angiogenesis. A high-throughput functional screening for the analysis of a whole-genome microRNA silencing library with regard to their phenotypic effect on endothelial cell proliferation as a key parameter, revealed several anti- and pro-proliferative microRNAs. Among those was miR-216a, a pro-angiogenic microRNA which is enriched in cardiac microvascular endothelial cells and reduced in expression under cardiac stress conditions. miR-216a null mice display dramatic cardiac phenotypes related to impaired myocardial vascularization and unbalanced autophagy and inflammation, supporting a model where microRNA regulation of microvascularization impacts the cardiac response to stress.
Background: Loss of stromal interaction molecule 1 (STIM1) expression in smooth muscle cells protects against ischemia-reperfusion (I/R) injury. Whether and how decreased STIM1 expression in cardiomyocytes (CM) impacts cardiac remodeling in response to I/R injury remains unknown.
Objective: To examine mechanisms by which decreased CM-STIM1 expression in the adult heart modulates cardiac function before and after I/R injury.
Heart failure (HF) is a complex clinical condition with symptoms that result from ineffective ejection of blood due to functional or structural impairment of the heart. The most common causes of HF include ischemic heart disease, myocardial infarction (MI), hypertension, and valvular heart disease (VHD). As HF progresses to advanced stages, interventions, like left ventricular assist devices (LVADs), become essential, especially for patients ineligible for heart transplantation.
DSG2, encoding desmoglein-2, is one of the causative genes of arrhythmogenic cardiomyopathy. We previously identified a homozygous DSG2 p.Arg119Ter stop-gain variant in a patient with juvenile-onset cardiomyopathy and advanced biventricular heart failure.
The processes of autophagy, including autophagosome formation, fusion of autophagosomes with lysosomes, and degradation of autophagosomes by lysosomes, are regulated by various mechanisms. We recently found that treatment with resveratrol, an activator of the NAD-dependent protein deacetylase Sirtuin-1 (SIRT1), in a mouse model prevented autophagosome accumulation in the heart with high mTORC1 activity. In this study, we investigated whether SIRT1 mediates the effects of resveratrol on autophagosome elimination using a cardiomyocyte model.
Department of Cardiovascular Biomedicine, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano 1, Col. Belisario Domínguez-Sección XVI, Tlalpan, 14080, Mexico City, Mexico.
Cardiomyocyte senescence plays a crucial role in the pathophysiology of age-related cardiovascular disease. Senescent cells with impaired contractility, mitochondrial dysfunction, and hypertrophic growth accumulate in the heart during aging, contributing to cardiac dysfunction and remodeling. Mitochondrial dynamics is altered in aging cells, leading to changes in their function and morphology.
