ORIGIN OF EXTRACELLULAR-MATRIX SYNTHESIS DURING CORONARY REPAIR

Background Coronary injury triggers differentiation of activated adven titial fibroblasts to myofibroblasts, which may contribute to neointim al formation and vascular remodeling. Accordingly, the purpose of this study was to examine the cellular origin of the enhanced synthesis of extracellular matrix proteins during coronary repair. Methods and Res ults The time course and localization of collagen and elastin expressi on were examined by in situ hybridization and immunohistochemistry in porcine coronary arteries after balloon-induced injury. ProcolIagen-al pha(1)(I) transcripts and intracellular type I procollagen protein inc reased in the adventitia within 2 days after injury. This was followed by a sustained synthesis of type I procollagen in neointima beginning at 7 days and the extracellular accumulation of type I collagen in bo th layers. The origin of synthetic cells was further examined by coloc alization of type I procollagen and bromodeoxyuridine labeling to acti vated adventitial cells, which translocated to neointima. Neointimal c ells exhibited sustained synthetic activity manifested by the presence of type I procollagen and elastin at 3 months after injury. In contra st, the media showed only minor changes in the synthesis of collagen o r elastin throughout coronary repair. Conclusions Activated adventitia l fibroblasts are endowed with synthetic capabilities after coronary i njury. They express type I procollagen, with some of them translocatin g to the intima, where they continue to synthesize procollagen. The ac cumulation of type I collagen is evident in the adventitia and neointi ma, whereas elastin accumulates mainly in neointima. These findings su pport the involvement of adventitial fibroblasts in coronary repair an d remodeling after endoluminal injury.