GLYCATED SERUM STIMULATION OF MACROPHAGES IN GK-RAT AND STREPTOZOTOCIN-RAT FOR THE PROLIFERATION OF PRIMARY CULTURED SMOOTH-MUSCLE CELLS OFTHE AORTA

The purpose of this study was to investigate the actions of intraperit oneal macrophages and aortic endothelial cells (EC) as the cause of pr oliferation of primary cultured smooth muscle cells (SMC) of the aorta in non-insulin-dependent diabetes mellitus (NIDDM) models, including spontaneously diabetic GK and streptozotocin-diabetic Wistar rats. Con ditioned medium derived from macrophages of GK rats increased prolifer ation of SMC in Wistar rats to a greater extent when compared to norma l Wistar rats in conditioned medium. Serum of both GK rats and of Wist ar rats which was previously exposed to 16.7 and 25 mM glucose (glycat ed serum) activated normal macrophages, enhancing SMC proliferation. H owever, glycated serum and high concentrations of glucose did not affe ct directly the proliferation of SMC. Conditioned medium from EC of st reptozotocin-Wistar rats enhanced SMC proliferation. The enhancing act ivity of EC in diabetic rats was mimicked by conditioned medium from g lycated EC but not from EC treated with the diabetic rat serum nor gly cated bovine serum albumin. Cholesterol (39 mu g/ml) potentiated the a ction of glycated serum on macrophages, but neither the action of norm al macrophages nor the direct action of SMC was affected. Both the act ions of glycated serum and cholesterol were inhibited by a polyclonal platelet-derived growth factor-BE antibody. However, low density lipop rotein (LDL), acetylated LDL and oxidized LDL (25 mu g/ml) did not pot entiate the action of glycated serum. These results demonstrate that g lycated serum in the NIDDM model predominantly activated macrophages, resulting in proliferation of SMC by the release of platelet-derived g rowth factor-BE. Cholesterol potentiated the actions of glycated serum on macrophages. (C) 1998 Elsevier Science B.V. All rights reserved.