Origin of extracellular matrix synthesis during coronary repair.

BACKGROUND

Coronary injury triggers differentiation of activated adventitial fibroblasts to myofibroblasts, which may contribute to neointimal 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 RESULTS

The time course and localization of collagen and elastin expression were examined by in situ hybridization and immunohistochemistry in porcine coronary arteries after balloon-induced injury. Procollagen-alpha 1(I) transcripts and intracellular type I procollagen protein increased 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 both layers. The origin of synthetic cells was further examined by colocalization of type I procollagen and bromodeoxyuridine labeling to activated adventitial cells, which translocated to neointima. Neointimal cells exhibited sustained synthetic activity manifested by the presence of type I procollagen and elastin at 3 months after injury. In contrast, the media showed only minor changes in the synthesis of collagen or elastin throughout coronary repair.

CONCLUSIONS

Activated adventitial fibroblasts are endowed with synthetic capabilities after coronary injury. They express type I procollagen, with some of them translocating to the intima, where they continue to synthesize procollagen. The accumulation of type I collagen is evident in the adventitia and neointima, whereas elastin accumulates mainly in neointima. These findings support the involvement of adventitial fibroblasts in coronary repair and remodeling after endoluminal injury.