Mechanism of cell death of endothelial cells regulated by mechanical forces

Cell death of endothelial cells (ECs) is a common devastating consequence of various vascular-related diseases. Atherosclerosis, hypertension, sepsis, diabetes, cerebral ischemia and cardiac ischemia/reperfusion injury, and chronic kidney disease remain major causes of morbidity and mortality worldwide, in which ECs are constantly subjected to a great amount of dynamic changed mechanical forces including shear stress, extracellular matrix stiffness, mechanical stretch and microgravity. A thorough understanding of the regulatory mechanisms by which the mechanical forces controlled the cell deaths including apoptosis, autophagy, and pyroptosis is crucial for the development of new therapeutic strategies. In the present review, experimental and clinical data highlight that nutrient depletion, oxidative stress, tumor necrosis factor-alpha, high glucose, lipopolysaccharide, and homocysteine possess cytotoxic effects in many tissues and induce apoptosis of ECs, and that sphingosine-1-phosphate protects ECs. Nevertheless, EC apoptosis in the context of those artificial microenvironments could be enhanced, reduced or even reversed along with the alteration of patterns of shear stress. An appropriate level of autophagy diminishes EC apoptosis to some extent, in addition to supporting cell survival upon microenvironment challenges. The intervention of pyroptosis showed a profound effect on atherosclerosis. Further cell and animal studies are required to ascertain whether the alterations in the levels of cell deaths and their associated regulatory mechanisms happen at local lesion sites with considerable mechanical force changes, for preventing senescence and cell deaths in the vascular-related diseases.