Expression of PDGF-A, TGFb and VCAM-1 during the developmental stages of experimental atherosclerosis

Purpose:A considerable number of growth factors, cytokines, and adhesion mo lecules are implicated in the development of atherosclerotic lesions. These molecules interact in a complex network influencing the evolution of sever al processes, such as lipid metabolism, cellular proliferation and tissue r epair. The aim of this study was to evaluate the expression of the growth f actors PDGF-A, and TGFb, and the adhesion molecule VCAM-1 in the sequential steps of experimental atherogenesis. Methods: Forty-two New Zealand white male rabbits were divided into 4 groups. The group A rabbits (n = 8) receiv ed normal diet and served as control animals. The remaining groups were fed with a diet enriched with 1% cholesterol and 6% corn oil. The rabbits of g roup B (n = 9) were sacrificed 1 month after the beginning of the study, of group C (n = 15) after 2 months and of group D (n = 10) after 3 months. In tissue sections of the aortic arch the antibodies of the prementioned fact ors were detected immunohistochemically. Results: In group A only TGFb and PDGF-A were detectable. In lesions of the first month PDGF-A expression was high but declined towards the third month. VCAM-1 expression was getting m ore intense up to the second month and subsided thereafter. TGFb expression intensified towards the third month. Changes in the expression of these fa ctors were statistically significant. Conclusion: PDGF-A, responsible for t he uncontrollable growth of smooth muscle cells, and VCAM-1, regulating mon ocyte recruitment in the intima, acts mainly during the early stages of ath erogenesis. TGFb, one of the main factors controlling the formation of conn ective tissue matrix, has a gradually increasing expression towards the thi rd month contributing probably to the fibrous plaque formation. Copyright ( C) 2001 S. Karger AG, Basel.