The effect of exercise-induced shear stress on the endothelium in health and disease

Cardiovascular disease is the leading cause of mortality worldwide, and one of the underlying conditions that causes this is atherosclerosis. Exercise could be a potential therapy in preventing or reversing atherosclerosis by increasing shear stress to areas susceptible to developing plaques. The aim of this thesis was to assess exercise-induced changes to shear stress pat-terns and magnitudes in arteries vulnerable to atherosclerosis and how that impacts the endothelial phenotype in vivo and in vitro. Using cardiac MRI and supine cycling exercise, tWSS in the thoracic aorta increased 10% in healthy participants and 15% in mitral regurgitation patients from rest. Shear stress was assessed by ultrasound in the common femoral artery of healthy participants during continuous and interval supine cycling exercise. Antero-grade shear stress was higher in the interval protocol compared to the con-tinuous (P<0.05), however there was no difference in FMD pre- to acutely post-exercise for either protocol (P>0.05). The in vivo shear stress from the common femoral artery for each exercise protocol was applied in vitro to HCAEC and the gene expression analysed by qRT-PCR. There was no dif-ference in gene expression between each protocol however eNOS expres-sion increased from 2-24 hours post-exercise (P<0.05), and MCP-1 and ICAM-1 both decreased from 2-24 hours post-exercise (P<0.05). The results of this thesis have shown that shear stress can be increased in areas of ar-teries that are susceptible to developing atherosclerosis and this provides a positive effect on endothelial phenotype by increasing anti-inflammatory gene expression, and decreasing inflammatory gene expression over time.