Exercise-Induced Laminar Blood Flow Maintains Vascular Function by Enhanced Endothelial Homeostasis

Abstract

PURPOSE: Laminar blood flow is known to play a critical role in maintaining endothelial homeostasis in blood vessels. It exerts a shear stress on the endothelial cells (ECs), which is essential for the regulation of various vascular functions. In this study, the effects of laminar blood flow-induced enhanced endothelial homeostasis on the maintenance of vascular function were investigated. METHODS: Human umbilical vein endothelial cells (HUVECs) were employed to study gene expression associated with vessel dilation and angiogenesis in response to varying shear stress levels. To assess angiogenesis, experimental mice participated in voluntary wheel running for 16 weeks. To evaluate the vascular autophagic function, the six weeks old C57BL/6 mice underwent an hour of forced treadmill running for 10 weeks. The resulting gene expression was evaluated through western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Disturbed flow resulting from partial ligation surgery in the mice’s carotid artery led to a decrease in angiogenic capacity compared to the laminar flow observed in ex vivo sprouting assays. Cultured HUVECs exhibited a significant increase in VEGF expression when exposed to increased durations of 20 dyne/cm² laminar shear stress (LSS). Following a 10-week treadmill exercise regimen, ECs in the carotid arteries of mice showed a significant increase in the expression of autophagic genes, such as LC3II, Atg3, and Atg7, which was not observed in smooth muscle cells (SMCs). LSS was found to boost the expression of both total and phosphorylated eNOS, genes involved in vascular dilation regulation, specifically in ECs. CONCLUSIONS: These findings suggest that laminar blood flow sustains vascular function, such as angiogenic capacity, through the enhancement of endothelial homeostasis.