SOMATOSTATIN ANALOG LANREOTIDE INHIBITS MYOCYTE REPLICATION AND SEVERAL GROWTH-FACTORS IN ALLOGRAFT ARTERIOSCLEROSIS

Chronic rejection is the most common reason for late loss of a transpl ant. The molecular mechanism of chronic rejection is not known and the re is no treatment for this disorder. The characteristic histological feature in chronic rejection is increased smooth muscle cell replicati on in the vascular wall, leading to allograft arteriosclerosis. In thi s study we demonstrate that nonimmunosuppressed rat aortic allografts undergoing chronic rejection synthesize increased quantitites of sever al smooth muscle cell growth-promoting substances in the vascular wall including interleukin-1, eicosanoids, and several peptide growth fact ors. Administration of a stable somatostatin analog lanreotide, BIM 23 014, strongly inhibits myocyte proliferation in the allograft in vivo. It has no inhibitory effect on the proliferation of smooth muscle cel ls in vitro. Concomitantly, the locally produced peptide growth factor s, i.e., epidermal growth factor, insulin-like growth factor 1, and BB -isomer of platelet-derived growth factor, but not other mediators of inflammation, are significantly reduced. The results suggest that grow th factors are the main effector molecules leading to myocyte prolifer ation in allograft arteriosclerosis and that allograft arteriosclerosi s (chronic rejection) may be specifically inhibited by lanreotide admi nistration.