New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death

Abstract

Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals and metabolites in the circulatory system. The senescence and death of ECs are not only adverse outcomes, but also causal contributors to endothelial dysfunction, an early risk marker of atherosclerosis. The pathophysiological process of EC senescence involves both structural and functional changes and has been linked to various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, and aberrant metabolite sensing and signaling. Multiple forms of EC death have been documented in atherosclerosis, including autophagic cell death, apoptosis, pyroptosis, NETosis, necroptosis, and ferroptosis. Despite this, the molecular mechanisms underlying EC senescence or death in atherogenesis are not fully understood. To provide a comprehensive update on the subject, this review examines the historic and latest findings on the molecular mechanisms and functional alterations associated with EC senescence and death in different stages of atherosclerosis.

Salvianolic acid A alleviates H2O2-induced endothelial oxidative injury via miR-204-5p

“…Endothelial cells are directly exposed to endogenous danger signals and metabolites in the circulatory system. Endothelial senescence and death associated EC dysfunction are widely recognized to be associated with vascular diseases such as atherosclerosis, hypertension and hyperlipidaemia and is a common early event in CVD 25,26 . Thus, research on EC senescence and death could accelerate the discovery of more effective drugs for the treatment of vascular diseases.…”

Endoplasmic reticulum stress-mediated cell death in cardiovascular disease

“…Various cell deaths present in endothelial cells in atherosclerosis, such as apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis. 146 Moderate autophagy plays a positive role in atherosclerosis, and both excessive autophagy and absence of autophagy lead to endothelial cell death and plaque instability. In atherosclerosis, iron overload and oxidized low-density lipoprotein induce lipid peroxidation, which triggers ferroptosis, ultimately leading to endothelial dysfunction and plaque instability.…”

Targeting vascular senescence in cardiovascular disease with aging

“…Vascular aging, a predictor of cardiovascular diseases such as hypertension, aortic aneurysms, and atherosclerosis [57] , is characterized by reduced endothelium-dependent dilation and increased arterial stiffness. Vascular aging is also associated with elevated systolic blood pressure, decreases in diastolic pressure, and increased central venous pressure [4] .…”