Rakugi H, Jacob H J, Krieger J E, Ingelfinger J R, Pratt R E
Falk Cardiovascular Research Center, Stanford University School of Medicine, Calif 94305-5246.
Circulation. 1993 Jan;87(1):283-90. doi: 10.1161/01.cir.87.1.283.
Angiotensin II promotes growth of vascular smooth muscle cells in vitro via the autocrine production of growth factors such as platelet-derived growth factor, basic fibroblast growth factor, and transforming growth factor-beta. Furthermore, experimental studies have demonstrated that angiotensin infusion can enhance smooth muscle proliferation after balloon injury in vivo. Consistent with this, angiotensin converting enzyme inhibitors have been shown to prevent myointimal proliferation. The origin of vascular angiotensin that participate in this process is of interest. We have demonstrated the presence of angiotensinogen messenger RNA (mRNA) in the adventitial and medial layers of the rat aorta and have speculated that local angiotensinogen production may play an important role during myointimal proliferation. To provide further evidence toward this hypothesis, we compared the localization and expression of angiotensinogen mRNA in control and balloon injured vessels using in situ hybridization.
Abdominal aorta of Sprague-Dawley rats were studied before or after injury with a balloon catheter. Neointimal hyperplasia developed as documented morphologically by a progressive increase in the ratio of neointimal to medial thickness from 0.17 at 1 week to 1.17 at 6 weeks after injury. Angiotensinogen mRNA was detected clearly in the adventitia and media of control and injured aorta. However, at 1 week after injury, the medial-to-adventitial angiotensinogen mRNA ratio was higher in the injured aorta, suggesting increased gene expression in the media compared with control. Of potential importance, angiotensinogen mRNA was also detected in the neointima of the injured aorta, and this was also highest at 1 week after injury.
These data are consistent with the hypothesis that balloon injury leads to activation of the vascular renin-angiotensin system, which may participate in the myointimal proliferation.
血管紧张素II通过自分泌生长因子（如血小板衍生生长因子、碱性成纤维细胞生长因子和转化生长因子-β）在体外促进血管平滑肌细胞生长。此外，实验研究表明，输注血管紧张素可增强体内球囊损伤后的平滑肌增殖。与此一致的是，血管紧张素转换酶抑制剂已被证明可预防肌内膜增殖。参与这一过程的血管紧张素的来源备受关注。我们已证实在大鼠主动脉的外膜和中膜层存在血管紧张素原信使核糖核酸（mRNA），并推测局部血管紧张素原的产生可能在肌内膜增殖过程中起重要作用。为进一步证实这一假说，我们采用原位杂交技术比较了对照血管和球囊损伤血管中血管紧张素原mRNA的定位和表达。
研究了经球囊导管损伤前后的Sprague-Dawley大鼠腹主动脉。损伤后新内膜增生形成，形态学上表现为损伤后1周时新内膜与中膜厚度之比从0.17逐渐增加至6周时的1.17。在对照主动脉和损伤主动脉的外膜和中膜中均清晰检测到血管紧张素原mRNA。然而，损伤后1周，损伤主动脉中膜与外膜血管紧张素原mRNA的比值高于对照，提示与对照相比中膜基因表达增加。具有潜在重要性的是，在损伤主动脉的新内膜中也检测到血管紧张素原mRNA，且在损伤后1周时也最高。
这些数据与球囊损伤导致血管肾素-血管紧张素系统激活的假说一致，该系统可能参与肌内膜增殖。
