VASCULAR INJURY INDUCES ANGIOTENSINOGEN GENE-EXPRESSION IN THE MEDIA AND NEOINTIMA

Background. 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. Methods and Results. 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. Conclusions. These data are consistent with the hypothesis thal balloon injury leads to activation of the vascular renin-angiotensin system, which may participate in the myointimal proliferation.