Diabetic dyslipidaemia is associated with alterations in eNOS, caveolin-1 and endothelial dysfunction in streptozotocin treated rats.

BackgroundDiabetes is a complex progressive disease characterized by chronic hyperglycaemia and dyslipidaemia associated with endothelial dysfunction. Oxidized LDL (Ox-LDL) is elevated in diabetes and may contribute to endothelial dysfunction. The aim of this study was to relate the serum levels of Ox-LDL with endothelial dysfunction in streptozotocin (STZ)-diabetic rats and to further explore the changes in endothelial nitric oxide synthase (eNOS) and caveolin-1 (CAV-1) expression in primary aortic endothelial cells. MethodsDiabetes was induced with a single intraperitoneal injection of STZ in male Wistar rats. During the hyperglycaemic diabetes state serum lipid markers, aortic relaxation and aortic endothelial cell eNOS and CAV-1 protein expressions were measured. ResultsElevated serum Ox-LDL (STZ 148678.1pg/mL vs control 732.6 +/- 160.6pg/mL, P<.05) was associated with hyperglycaemia (STZ 29 +/- 0.9mmol/L vs control: 7.2 +/- 0.2mmol/L, P<.001) and hypertriglyceridaemia (STZ 9.0 +/- 1.5mmol/L vs control: 3.0 +/- 0.3mmol/L, P<.01) in diabetic rats. A significant reduction was observed in STZ-diabetic aortic endothelial cell eNOS and CAV-1 of 40% and 30%, respectively, accompanied by a compromised STZ-diabetic carbachol-induced vasodilation (STZ 29.6 +/- 9.3% vs control 77.2 +/- 2.5%, P<.001). ConclusionsThe elevated serum Ox-LDL in hyperglycaemic STZ-diabetic rats may contribute to diabetic endothelial dysfunction, possibly through downregulation of endothelial CAV-1 and eNOS.