Mitogenic activity in human atherosclerotic lesions

Focal smooth muscle cell proliferation is a key event in atherogenesis, but the stimulating factors are unknown, and there is little information on the occurrence of growth promoting factors in the arterial wall. We have tested extracts of human aortic intima for stimulation of DNA synthesis, using the chick chorioallantoic membrane (CAM) assay in an attempt to avoid artifacts arising with cultured cells. Consistently high levels of stimulation were obtained with early proliferative (gelatinous) lesions (mean DNA synthesis 188% of control, n = 6) and slightly more advanced transitional lesions (mean 160%, n = 4); results with mature fibrous plaques were variable (range 120-182%, n = 3). Significant stimulation was also given by four of eleven samples of apparently lesion-free intima. Intima contains fibrinogen and a range of fibrinogen and fibrin degradation products (FRA) and preliminary fractionation experiments suggest that activity may reside in the FRA fraction. Serum does not stimulate DNA synthesis in the CAM; extract activity was retained in FRA-containing fractions after removal of most serum proteins by affinity chromatography, but was mainly lost from serum protein-containing fractions after removal of FRA.