Increased platelet-derived mitogenic activity in plasma of young patients with coronary atherosclerosis

The early state of atherosclerosis is characterized by a nodular proliferation of smooth muscle cells in the arterial intima. It has been suggested that this proliferation is initiated by platelet-derived growth factor (PDGF) released from aggregating platelets in connection with endothelial injury. In the present study platelet reactivity and mitogenic activity of plasma and serum were compared in young male survivors of myocardial infarction with angiographically demonstrable coronary atherosclerosis and in healthy subjects of similar age. Young post-infarction patients with coronary atherosclerosis had lower ED50 values of ADP-induced platelet aggregation. Furthermore plasma and serum from the patients contained increased amounts of mitogenic activity. Experiments using antibodies against platelet-derived growth factor indicated that the increase in mitogenic activity represented elevated concentrations of free PDGF growth factor in plasma. The results raise the possibility of a connection between increased levels of free PDGF and the proliferative reaction that characterizes early lesion progression.