Biomechanical Regulation of Endothelial Phenotype

Endothelium is the tissue that forms the inner surface of all blood vessels. This monocellular layer detects and reacts to chemical and physical signals, in particular shear stress elicited by blood flow. Endothelium controls health and function of blood vessels, thus plays a key role in the development of cardiovascular diseases. Regular exercise increases shear stress which, together with balanced diet, maintains a functional and healthy endothelium. In contrast, risk factors for cardiovascular diseases such as a sedentary lifestyle and exposure to excessive cigarette smoke, high level of sugar, fat and cholesterol cause damage of the endothelium. In addition, ageing induces endothelial damage through a process called senescence. Together, these risk factors and ageing cause changes in fibrotic signalling (transforming growth factor-β) and oxidative stress in endothelial cells, which underlie unhealthy endothelium. Interestingly, shear stress can suppress and partially reverse the damage caused by these risk factors and ageing. This thesis aims to delineate how the endothelium detects and reacts to transforming growth factor-β, oxidative stress (chemical signals) and shear stress (physical signal), as well as to understand the role of ageing in this context. We showed that high shear stress protects the endothelium from the detrimental effects of transforming growth factor-β and oxidative stress. Interestingly, ageing does not hamper the ability of endothelium to detect and react to high shear stress. Therefore, damage results from ageing can be prevented if the endothelium is exposed to high shear stress continuously. This means that regular exercise which maintains shear stress at an appropriate level can prevent damage on endothelium caused by transforming growth factor-β, oxidative stress and ageing, thus prevents the development of cardiovascular diseases