PLATELET-DERIVED GROWTH-FACTOR BB MEDIATED REGULATION OF 12-LIPOXYGENASE IN PORCINE AORTIC SMOOTH-MUSCLE CELLS

Platelet-derived growth factor BE (PDGF) is a potent mitogen and chemo attractant for vascular smooth muscle cells (VSMC). In the present stu dy, we have examined the effects of PDGF on the 12-lipoxygenase (12-LO ) pathway of arachidonate metabolism in porcine aortic VSMC (PVSMC). T he rationale for this is previous studies showing that LO products hav e growth and chemotactic effects in VSMC and that another VSMC growth factor, angiotensin II, is a potent positive regulator of 12-LO activi ty and expression. We observed that PDGF causes a significant increase in the formation of the 12-LO product, 12-hydroxyeicosatetraenoic aci d (12-HETE) in PVSMC. In addition, PDGF also markedly increased leukoc yte-type 12-LO messenger RNA and protein expression. PDGF-induced PVSM C migration was inhibited significantly by two LO blockers but not by a cyclooxygenase blocker. Furthermore, although the proliferative effe cts of PDGF on PVSMC were not altered by cell culture under hyperglyce mic conditions (25 mM glucose, HG), the chemotactic effects of PDGF as well as those of 10% fetal calf serum were significantly greater in c ells cultured in HG as compared to normal glucose conditions (5.5 mM), thus indicating a potential new mechanism for the accelerated cardiov ascular disease usually observed in diabetes. These results indicate a novel mechanism for the biological effects of PDGF in leading to card iovascular disease. (C) 1996 Wiley-Liss, Inc.