Hypertension. 2001;38:581-587
doi: 10.1161/hy09t1.096249
doi: 10.1161/hy09t1.096249
(Hypertension. 2001;38:581.)
© 2001 American Heart Association, Inc.
Cardiovascular Biology |
Vascular Remodeling in Hypertension
Roles of Apoptosis, Inflammation, and Fibrosis
Metabolic Research Unit/Diabetes Center, University of California at San Francisco (H.D.I.); and Clinical Research Institute of Montreal (E.L.S.), Montreal, Québec, Canada
Correspondence to Hope D. Intengan, PhD, Box 0540, Metabolic Research Unit/Diabetes Center, University of California at San Francisco, San Francisco, CA 94143. E-mail intengh{at}itsa.ucsf.edu
Abstract
Abstract—— Remodeling of large and small arteries contributes to the development and complications of hypertension. The focus of this review is some of the mechanisms involved in the remodeling of small arteries in hypertension. In hypertension, changes in small artery structure are basically of 2 kinds: (1) inward eutrophic remodeling, in which outer and lumen diameters are decreased, 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 and media/lumen ratio. Growth, apoptosis, inflammation, and fibrosis contribute to vascular remodeling in hypertension. Apoptosis is gene-regulated cell death, with minimal membrane disruption and inflammation, that counters cell proliferation and fine-tunes developmental growth. Apoptosis has been reported in hypertension to be both increased and decreased in different tissues, including blood vessels. Inflammation, which may be low grade, probably plays an important role in triggering fibrosis in cardiovascular disease and hypertension. Vascular fibrosis entails accumulation of collagen, fibronectin, and other extracellular matrix components in the vessel wall and is an important aspect of extracellular matrix remodeling in hypertension. Associated with this, there may be increases in cell-matrix attachment sites (integrins) and changes in their topographical localization that may modulate arterial structure. Imbalance in matrix metalloproteinase/tissue inhibitors of metalloproteinases may contribute to alteration in collagen turnover 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 remodeling of small arteries may initially be adaptive, but eventually it becomes maladaptive and compromises organ function, contributing to cardiovascular complications of hypertension.
Key Words: arteries • apoptosis • inflammation • fibrosis • collagen • muscle, smooth
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|
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