Aging is a major non-modifiable risk factor underlying hypertension and associated cardiovascular disease. With aging, the vasculature undergoes structural, functional and mechanical alterations characterized by endothelial dysfunction, media thickening, reduced distensibility, and arterial stiffening. Many of these processes are associated with activation of the renin angiotensin aldosterone system (RAAS), which is characteristically associated with the pathophysiology of hypertension. In particular Ang II, through the AT1 receptor, and aldosterone through the mineralocorticoid receptor, activate pro-inflammatory and pro-fibrotic signaling pathways that lead to vascular fibrosis, extracellular matrix (ECM) deposition, arterial remodelling, perivascular inflammation and hyperreactivity. These processes are also associated with aging and are amplified by hypertension. Molecular mechanisms underlying these events include increased expression and activation of matrix metalloproteinases, activation of transforming growth factor1/SMAD signalling, upregulation of galectin-3, activation of aging signaling pathways, eg p66Shc, c-Src, and oxidative stress. Fundamental to these processes is phenotypic switching of vascular smooth muscle cells from a contractile to de-differentiated state. This involves epigenetic changes and alterations in the vascular proteome. Complex interplay between the “aging process” and prohypertensive factors, including Ang II and aldosterone, result in accelerated vascular remodelling and fibrosis and increased arterial stiffness, which is typically observed in hypertension. Because the vascular phenotype in a young hypertensive individual resembles that of an elderly otherwise healthy individual, the notion of “early” or “premature” vascular aging is frequently used to describe hypertension-associated vascular disease. This presentation discusses the vascular phenotype in aging and hypertension and the role of the RAAS. In addition novel molecular mechanisms, focusing on oxidative stress and the vascular proteome will be highlighted.
