Diabetic state-modified macrophages in GK rat release platelet-derived growth factor-BB for tube formation of endothelial cells in rat aorta

Abstract

Cultured peritoneal macrophages (Mø) of GK rats, a non insulin-dependent diabetes mellitus model established from normal Wistar rats, increased the tube formation of aortic endothelial cells (EC). A polyclonal anti-platelet-derived growth factor (PDGF)-BB (0.21–3.3 μg/ml) inhibited (by 66.5 ± 6.6%) the tube-forming activity of conditioned medium (CM) from Mø in diabetic GK rats, but not that in age-matched normal Wistar rats. A polyclonal anti-interleukin (IL)-α (0.16–0.33%) also inhibited (by 37.7 ± 5.8%) the activity of diabetic Mø-CM, and its inhibitory effect was smaller than that of anti-PDGF-BB. A monoclonal anti-basic fibroblast growth factor (bFGF) (0.6–60 ng/ml) inhibited the activities of CM from both Mø, respectively. The tube-forming activity of the normal MO-CM was increased by the serum isolated from the diabetic GK rat more than by that from the age-matched normal Wistar rat. The activity of normal MO-CM was also increased by 16.7-50 mM glucose-exposed serum. These tube-forming activities of the CM of Mø stimulated by diabetic serum and by the high concentration of glucose-treated serum were completely inhibited by anti-PDGF-BB. In conclusion, PDGF-BB was selectively released from the diabetic state-modified Mø in the GK rat to increase tube formation, suggesting a key role in the cause of angiogenesis. The diabetic state-induced activation may depend on advanced glycosylation endproducts produced in the serum in the diabetic rat.