Pratt R E
Division of Cardiovascular Medicine, Stanford University School of Medicine, California, USA.
Blood Press Suppl. 1996;2:6-9.
Abnormal growth of vascular smooth-muscle cells is a characteristic of many cardiovascular diseases. This abnormal growth occurs during hypertension-induced vascular hypertrophy, during the development of an atherosclerotic lesion, and during the development of a restenotic lesion following angioplasty. It is becoming increasingly apparent that among the many factors that may influence vascular structure, angiotensin may play a major role. Angiotensin-converting enzyme (ACE) inhibitors decrease hypertension-induced vascular hypertrophy, and, in many animal models, these inhibitors block the development of atherosclerosis and the development of an injury-induced neointimal lesion. Evidence suggests that the local production of angiotensin via tissue-converting enzyme may play an important role in these growth effects. We have demonstrated in animal models that injured vessels express high levels of ACE. Moreover, we have shown that the ability of an ACE inhibitor to block neointimal development correlates better with its ability to inhibit tissue ACE than with its ability to block circulating ACE. The role of angiotensin in human atherosclerosis is not clear. In an immunohistochemical study of human coronary arteries, we have obtained evidence that ACE is present within the atherosclerotic plaque, associated with regions of macrophage clustering. Moreover, in cell culture, monocytes induced to differentiate into macrophages express high levels of ACE. Treatment of these cells with acetylated low density lipoproteins results in a further increase in ACE expression. These results support the hypothesis that ACE may play a role in the development of atherosclerosis. Further studies, however, are required to precisely define this role.
血管平滑肌细胞的异常生长是许多心血管疾病的一个特征。这种异常生长发生在高血压诱导的血管肥厚过程中、动脉粥样硬化病变发展过程中以及血管成形术后再狭窄病变发展过程中。越来越明显的是，在可能影响血管结构的众多因素中，血管紧张素可能起主要作用。血管紧张素转换酶（ACE）抑制剂可减轻高血压诱导的血管肥厚，并且在许多动物模型中，这些抑制剂可阻止动脉粥样硬化的发展以及损伤诱导的新生内膜病变的发展。有证据表明，通过组织转换酶局部产生的血管紧张素可能在这些生长效应中起重要作用。我们在动物模型中已证明，受损血管表达高水平的ACE。此外，我们还表明，ACE抑制剂阻断新生内膜发展的能力与其抑制组织ACE的能力相关性更好，而与其阻断循环ACE的能力相关性较差。血管紧张素在人类动脉粥样硬化中的作用尚不清楚。在一项对人类冠状动脉的免疫组织化学研究中，我们已获得证据表明，ACE存在于动脉粥样硬化斑块内，与巨噬细胞聚集区域相关。此外，在细胞培养中，诱导分化为巨噬细胞的单核细胞表达高水平的ACE。用乙酰化低密度脂蛋白处理这些细胞会导致ACE表达进一步增加。这些结果支持ACE可能在动脉粥样硬化发展中起作用这一假说。然而，需要进一步研究来精确界定这一作用。
