Physical Exercise Protects Against Endothelial Dysfunction in Cardiovascular and Metabolic Diseases

Abstract

Increasing evidence shows that endothelial cells play critical roles in maintaining vascular homeostasis, regulating vascular tone, inhibiting inflammatory response, suppressing lipid leakage, and preventing thrombosis. The damage or injury of endothelial cells induced by physical, chemical, and biological risk factors is a leading contributor to the development of mortal cardiovascular and cerebrovascular diseases. However, the underlying mechanism of endothelial injury remains to be elucidated. Notably, no drugs effectively targeting and mending injured vascular endothelial cells have been approved for clinical practice. There is an urgent need to understand pathways important for repairing injured vasculature that can be targeted with novel therapies. Exercise training-induced protection to endothelial injury has been well documented in clinical trials, and the underlying mechanism has been explored in animal models. This review mainly summarizes the protective effects of exercise on vascular endothelium and the recently identified potential therapeutic targets for endothelial dysfunction.

Keywords: Endothelium dysfunction; Exercise; Therapeutic targets; Vascular disease.

Fig. 1

Endothelium functions as an important endocrine organ. TXA2, thromboxane A2; TF, tissue factor; PAI, plasminogen activator inhibitor; PAF, platelet activating factor; TSP, thrombospondin; VWF, von Willebrand factor; AT-III, antithrombin III; TFPI, tissue factor pathway inhibitor; TM, thrombomodulin; t-PA, tissue plasminogen activator; PGI2, prostaglandin I2, also called prostacyclin; EDRF, endothelium derived relaxing factor; NO, nitric oxide; EDHF, endothelium-derived hyperpolarizing factor; CNP, c-type natriuretic peptide; ET-1, endothelin; ACE, angiotensin converting enzyme; EDCF1, endothelium-derived contracting factor 1; FGF, fibroblast growth factor; PDGF, platelet derived growth factor; TGF, transforming growth factor; IGF, insulin-like factor; IL-6, interleukin-6; IL-1β, interleukin-1β; MCP1, monocyte chemoattractant protein-1

Fig. 2

Risk factors impair endothelial function

Fig. 3

The underlying mechanism of the exercise in the protection of endothelial dysfunction

Fig. 4

miRNAs regulated by exercise in the protection of endothelial dysfunction