Cellular and Molecular Determinants of Arterial Aging

A number of key signaling pathways are highly relevant to early vascular aging. These are overviewed here to provide a context for understanding the initiation and progression of hypertension, arteriosclerosis, and atherosclerosis. The elements of the pathways include the following: cytoskeletal and contractile proteins; elastin and collagen networks; adhesion proteins and metalloproteinases; cytokines; reactive oxygen species; and NO bioavailability and the renin-angiotensin-aldosterone system. Activation of these pathways leads to a proinflammatory state and tissue oxidative stress, which in turn drives age-associated remodeling processes. A progressive decrease in plasticity and increase in reprogramming potential of vascular smooth muscle cells plays a complementary role, contributing to the increase in arterial stiffness and associated cardiovascular risk factors. These key signaling pathways have become the focus of modern aging research and their elucidation will undoubtedly provide a rich resource for the development of selective drugs that will interfere with these processes and aid in the prevention of the number one cause of death in the modern world.