Vascular fibrosis in aging and hypertension: Molecular mechanisms and clinical implications

Abstract Aging is the primary risk factor underlying hypertension and incident cardiovascular disease. With ageing the vasculature undergoes structural and functional changes characterised by endothelial dysfunction, wall thickening, reduced distensibility and arterial stiffening. Vascular stiffness results from fibrosis and extracellular matrix remodeling, processes that are associated with aging and amplified by hypertension. Some recently characterised molecular mechanisms underlying these processes include increased expression and activation of matrix metalloproteinases (MMPs), activation of TGFβ1/SMAD signaling, upregulation of galectin-3 and activation of pro-inflammatory and pro-fibrotic signaling pathways. These events can be induced by vasoactive agents, such as angiotensin II (Ang II), endothelin-1 (ET-1) and aldosterone, that are increased in the vasculature during aging and hypertension. Complex interplay between the ‘aging process’ and pro-hypertensive factors results in accelerated vascular remodelling and fibrosis, and increased arterial stiffness, 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 now often used to describe hypertension-associated vascular disease. Here, we review the vascular phenotype in ageing and hypertension focusing on arterial stiffness and vascular remodeling. We also highlight the clinical implications of these processes and discuss some novel molecular mechanisms of fibrosis and extracellular matrix reorganisation.