Injured arterial smooth muscle cells in culture release factors affecting viability and collagen secretion of new cultures.

Cultures of arterial smooth muscle cells were exposed to ultraviolet light, dimethylsulphoxide-soluble particles from cigarette smoke (DSP) and hypoxia. Hypoxia produced no lasting toxic effects but the other stimuli did. Serum free medium was conditioned by cells damaged by these stimuli and the effects on new smooth muscle cell cultures were studied. Hypoxia did not induce any transferable effects. Cells damaged by a standard concentration of DSP released factor(s) that reduced cell mass of new cultures by 25% compared to controls; cell death increased 23%, and DNA synthesis fell by 23% but collagen secretion was unchanged in absolute amounts. If correction for the smaller cell mass was performed, collagen secretion increased 46% while DNA synthesis was unchanged. The DSP induction of transferable cell injury was biphasically dose dependent, maximal effect being noted in the intermediate DSP levels. If ultraviolet light was used as stimulus, cell mass of secondary cultures fell by 32% and cell death increased 31%. Correction for the smaller cell mass showed that both DNA synthesis and collagen secretion were increased compared to controls, both by 61%. The transferable activity remained after dialysis but was completely destroyed by heating at 100 degrees C. The results are discussed in relation to the pathogenesis of atherosclerosis, and it is suggested that cell injury might lead to selection of more active cell clones that could contribute to the progression of atherosclerosis.