Apoptosis and angiogenesis: an evolving mechanism for fibrosis.

Fibrosis, seen in the liver, lung, heart, kidney, and skin, is a significant global disease burden. Currently, therapeutic treatment is limited, and the number of cases continues to grow. Apoptosis has been identified as a potential initiator and propagator of fibrosis. This review specifically examines the correlation between the presence of apoptotic cells and their effect on fibroblast phenotype and collagen metabolism in several different experimental models of fibrosis. Fibrosis in these models is generally preceded by robust angiogenesis and vascular regression, suggesting that the vascular apoptotic burden may be important to fibrotic outcomes. This review considers the emerging evidence that angiogenesis or vascular regression contributes to fibrosis and identifies initial vascular outgrowth or vascular apoptotic cell presence as possible regulators of fibrosis. A further understanding of the cellular mechanisms of fibrosis may suggest novel methods for the reduction of the fibrotic response and promotion of regeneration.