Intengan H D, Schiffrin E L
Metabolic Research Unit/Diabetes Center, University of California at San Francisco, USA.
Hypertension. 2001 Sep;38(3 Pt 2):581-7. doi: 10.1161/hy09t1.096249.
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.
大、小动脉的重塑参与了高血压的发生发展及并发症的形成。本综述的重点是高血压中小动脉重塑所涉及的一些机制。在高血压中，小动脉结构的改变基本有两种：（1）内向性营养型重塑，即外径和内径减小，中膜/管腔比值增加，中膜横截面积不变；（2）肥厚性重塑，即中膜增厚以侵占管腔，导致中膜横截面积和中膜/管腔比值增加。生长、凋亡、炎症和纤维化参与了高血压中的血管重塑。凋亡是基因调控的细胞死亡，细胞膜破坏和炎症轻微，可对抗细胞增殖并微调发育生长。据报道，在高血压中，不同组织（包括血管）中的凋亡既有增加也有减少。炎症可能程度较轻，在心血管疾病和高血压中触发纤维化可能起重要作用。血管纤维化需要胶原蛋白、纤连蛋白和其他细胞外基质成分在血管壁中积累，是高血压中细胞外基质重塑的一个重要方面。与此相关的是，细胞-基质附着位点（整合素）可能增加，其拓扑定位也可能发生变化，这可能调节动脉结构。基质金属蛋白酶/金属蛋白酶组织抑制剂的失衡可能导致胶原蛋白周转和细胞外基质重塑的改变。慢性血管收缩可能导致收缩的血管结构嵌入重塑的细胞外基质中，随着平滑肌细胞围绕较小的管腔重新排列，导致血管内向性重塑。小动脉由此产生的重塑最初可能是适应性的，但最终会变得适应不良并损害器官功能，导致高血压的心血管并发症。
