Powell J S, Rouge M, Müller R K, Baumgartner H R
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Basic Res Cardiol. 1991;86 Suppl 1:65-74.
Smooth muscle cell proliferation and formation of extracellular matrix in the intima of muscular arteries after vascular injury can lead to severe intimal hyperplasia and stenosis. Cilazapril reduces intimal hyperplasia induced by balloon catheterization of the rat carotid artery by 80%, and significantly decreases the surface area covered by proliferative lesions. We investigated the effects of angiotensin II (A II) on SMC proliferation in cell culture and A-II induction of selected growth factor or growth-related genes in SMC in culture: PDGF A chain, TGF-beta, thrombospondin, c-myc and c-fos, and compared the influence of cilazapril on these responses to A II. A-II induced SMC proliferation, stimulated mRNAs for c-myc and c-fos after 30 min, and stimulated mRNAs for PDGF A chain, TGF-beta, and thrombospondin somewhat later. The ACE inhibitor did not have detectable independent effects on the A-II induced proliferation or gene expression. Thus, these data support the conclusion that cilazapril suppresses SMC proliferation in vivo through the block of conversion of A I to A II, and that A II has a critical and central role in the control of the proliferative response after balloon catheter-induced vascular injury.
血管损伤后肌性动脉内膜中平滑肌细胞增殖及细胞外基质形成可导致严重的内膜增生和狭窄。西拉普利可使大鼠颈动脉球囊导管损伤所致的内膜增生减少80%，并显著降低增殖性病变覆盖的表面积。我们研究了血管紧张素II（A II）对细胞培养中平滑肌细胞增殖的影响，以及A II对培养的平滑肌细胞中所选生长因子或生长相关基因的诱导作用：血小板衍生生长因子A链（PDGF A链）、转化生长因子-β（TGF-β）、血小板反应蛋白、c-myc和c-fos，并比较了西拉普利对这些A II反应的影响。A II诱导平滑肌细胞增殖，30分钟后刺激c-myc和c-fos的mRNA表达，稍后刺激PDGF A链、TGF-β和血小板反应蛋白的mRNA表达。血管紧张素转换酶（ACE）抑制剂对A II诱导的增殖或基因表达没有可检测到的独立作用。因此，这些数据支持以下结论：西拉普利通过阻断AI向A II的转化来抑制体内平滑肌细胞增殖，且A II在球囊导管诱导的血管损伤后增殖反应的控制中起关键和核心作用。
