INDUCTION OF THE ACE AND PDGF GENE-EXPRES SION IN THE NEOINTIMA

Experimental studies have shown that the denudation of the endothelial layer of rat carotid arteries caused by balloon catheter injury leads to an extensive neointima proliferation. Due to the antiproliferative effects of angiotensin-converting enzyme (ACE)-inhibitors and angiote nsin-II antagonists observed in this model the participation of the re nin-angiotensin system (RAS) has been postulated. The aim of this stud y was to investigate the regulation of the ACE gene during proliferati ve processes. We therefore, removed the endothelial layer of the left Arteria carotis communis in rats by a balloon catheter, whereas the un injured contralateral carotid was used as control. The carotids were r emoved 2, 8, 14 and 21 days after the injury and histologically examin ated. Two days after injury vascular smooth muscle cell immigration in to the lumen of the vessel started. Proliferation of these cells was o bserved after 8 days and reduced the lumen by 25% after 2 weeks. In ad dition, the DNA content of the injured artery was significant elevated from the 8th day after the injury and continued to increase until day 14. In order to study the functions of the RAS and to characterize it s interaction with other growth factors, the ACE and platelet-derived growth factor-A chain (PDGF-A) mRNA expression was analyzed by quantit ative polymerase chain reaction (PCR) techniques. Two days after the i njury the ACE mRNA in the injured vessels was increased to 87% compare d to the uninjured control vessels. The maximum of difference was reac hed after 8 days at 92%, which was then followed by a decrease. The PD GF-A expression was not significantly elevated in the same time period . These results indicate a functional participation of the RAS during proliferative processes in this model.