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 transplant. The molecular mechanism of chronic rejection is not known and there is no treatment for this disorder. The characteristic histological feature in chronic rejection is increased smooth muscle cell replication in the vascular wall, leading to allograft arteriosclerosis. In this study we demonstrate that nonimmunosuppressed rat aortic allografts undergoing chronic rejection synthesize increased quantities of several smooth muscle cell growth-promoting substances in the vascular wall including interleukin-1, eicosanoids, and several peptide growth factors. Administration of a stable somatostatin analog lanreotide, BIM 23014, strongly inhibits myocyte proliferation in the allograft in vivo. It has no inhibitory effect on the proliferation of smooth muscle cells in vitro. Concomitantly, the locally produced peptide growth factors, 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 growth factors are the main effector molecules leading to myocyte proliferation in allograft arteriosclerosis and that allograft arteriosclerosis (chronic rejection) may be specifically inhibited by lanreotide administration.
Häyry
P
P
Transplantation Laboratory, University of Helsinki, Finland.
Räisänen
A
A
Ustinov
J
J
Mennander
A
A
Paavonen
T
T
D000818:Animals; D001011:Aorta / Q000637:transplantation; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002455:Cell Division / Q000187:drug effects; D006084:Graft Rejection; D006133:Growth Substances / Q000096:biosynthesis*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000031:analogs & derivatives*; D014184:Transplantation, Homologous
D006133:Growth Substances; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin