Gibbons G H
Molecular and Cellular Vascular Biology Research Laboratory, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Clin Cardiol. 1997 Nov;20(11 Suppl 2):II-18-25.
The ability of the vasculature to modify its geometry in accordance with conditions of its microenvironment--the process of vascular remodeling--is an important pathobiologic process common to vascular disorders such as atherosclerosis, restenosis after angioplasty, and hypertension. Vascular remodeling characterizes the natural history of atherosclerosis, contributes to increased vascular resistance, and may contribute to the clinical complications of hypertension. A growing body of evidence indicates that locally generated vasoactive substances such as angiotensin II and nitric oxide are important determinants of the natural history of vascular disease. In particular, angiotensin II may promote vascular lesion formation by increasing vascular cell population via increased cell growth and decreased programmed cell death, and it may also alter extracellular matrix composition. Thus, angiotensin II is a pleiotropic local mediator capable of modulating cell growth, programmed cell death, migration of vascular smooth muscle cells, and extracellular matrix modulation, all of which are biologic mechanisms of vascular remodeling and intimal formation. This is proposed to occur via a local tissue angiotensin system. Angiotensin II may also promote chronic hypertension by modulating the vascular redox state and promoting the catabolism of the endothelium-derived nitric oxide, an endogenous inhibitory vasodilator. Because angiotensin-converting enzyme (ACE) is strategically positioned to influence the activity of at least three local vasoactive systems--angiotensin II, nitric oxide, and bradykinin--blocking ACE with ACE inhibition may have profound effects on ventricular and vascular structure and function, and have particular efficacy in preventing the morbidity and mortality of vascular diseases such as hypertension and atherosclerosis.
脉管系统根据其微环境条件改变其几何形状的能力——血管重塑过程——是动脉粥样硬化、血管成形术后再狭窄和高血压等血管疾病共有的重要病理生物学过程。血管重塑是动脉粥样硬化自然病程的特征，导致血管阻力增加，并可能导致高血压的临床并发症。越来越多的证据表明，局部产生的血管活性物质如血管紧张素II和一氧化氮是血管疾病自然病程的重要决定因素。特别是，血管紧张素II可能通过增加细胞生长和减少程序性细胞死亡来增加血管细胞数量，从而促进血管病变形成，还可能改变细胞外基质成分。因此，血管紧张素II是一种多效性局部介质，能够调节细胞生长、程序性细胞死亡、血管平滑肌细胞迁移和细胞外基质调节，所有这些都是血管重塑和内膜形成的生物学机制。这被认为是通过局部组织血管紧张素系统发生的。血管紧张素II还可能通过调节血管氧化还原状态和促进内皮源性一氧化氮（一种内源性血管舒张抑制剂）的分解代谢来促进慢性高血压。由于血管紧张素转换酶（ACE）处于影响至少三种局部血管活性系统——血管紧张素II、一氧化氮和缓激肽——活性的关键位置，用ACE抑制剂阻断ACE可能对心室和血管结构与功能产生深远影响，并且在预防高血压和动脉粥样硬化等血管疾病的发病率和死亡率方面具有特殊疗效。
