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

This is the peer reviewed version of the following article: Yousif A. Shamsaldeen, Rosemary Ugur, Christopher D. Benham, and Lisa A. Lione, ‘Diabetic dyslipidaemia is associated with alterations in eNOS, caveolin‐1, and endothelial dysfunction in streptozotocin treated rats’, Diabetes Metabolism Research and Reviews, e2995, March 2018, which has been published in final form at https://doi.org/10.1002/dmrr.2995. Under embargo until 22 February 2019. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Background: Diabetes is a complex progressive disease characterised by chronic hyperglycaemia and dyslipidaemia associated with endothelial dysfunction. Oxidised 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 (ECs). Methods: Diabetes 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 ECs eNOS and CAV-1 protein expression was measured. Results: Elevated serum Ox-LDL (STZ 1486 ± 78.1 pg/ml vs control 732.6 ± 160.6pg/ml, p<0.05) was associated with hyperglycaemia (STZ 29 ± 0.9 mmol/L vs control: 7.2 ± 0.2 mmol/L, p<0.001) and hypertriglyceridemia (STZ 9.0 ± 1.5 mmol/L vs control: 3.0 ± 0.3 mmol/L, p<0.01) 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<0.001). Conclusions: The elevated serum Ox-LDL in hyperglycaemic STZ-diabetic rats may contribute to diabetic endothelial dysfunction, possibly through downregulation of endothelial CAV-1 and eNOS.Peer reviewe