Vascular remodeling in hypertension - Roles of apoptosis, inflammation, and fibrosis

Remodeling of large and small arteries contributes to the development and c omplications of hypertension. The focus of this review is some of the mecha nisms involved in the remodeling of small arteries in hypertension. In hype rtension, changes in small artery structure are basically of 2 kinds: (1) i nward eutrophic remodeling, in which outer and lumen diameters are decrease d, media/lumen ratio is increased, and cross-sectional area of the media is unaltered; and (2) hypertrophic remodeling, in which the media thickens to encroach on the lumen, resulting in increased media cross-sectional area a nd media/lumen ratio. Growth, apoptosis, inflammation, and fibrosis contrib ute to vascular remodeling in hypertension. Apoptosis is gene-regulated cel l death, with minimal membrane disruption and inflammation, that counters c ell proliferation and fine-tunes developmental growth. Apoptosis has been r eported in hypertension to be both increased and decreased in different tis sues, including blood vessels. Inflammation, which may be low grade, probab ly plays an important role in triggering fibrosis in cardiovascular disease and hypertension. Vascular fibrosis entails accumulation of collagen, fibr onectin, and other extracellular matrix components in the vessel wall and i s an important aspect of extracellular matrix remodeling in hypertension. A ssociated with this, there may be increases in cell-matrix attachment sites (integrins) and changes in their topographical localization that may modul ate arterial structure. Imbalance in matrix metalloproteinase/tissue inhibi tors of metalloproteinases may contribute to alteration in collagen turnove r and extracellular matrix remodeling. Chronic vasoconstriction may lead to embedding of the contracted vessel structure in a remodeled extracellular matrix, contributing to the inward remodeling of the blood vessel as smooth muscle cells are rearranged around a smaller lumen. The resulting remodeli ng of small arteries may initially be adaptive, but eventually it becomes m aladaptive and compromises organ function, contributing to cardiovascular c omplications of hypertension.