Premium
Diabetic dyslipidaemia is associated with alterations in eNOS, caveolin‐1, and endothelial dysfunction in streptozotocin treated rats
Author(s) -
Shamsaldeen Yousif A.,
Ugur Rosemary,
Benham Christopher D.,
Lione Lisa A.
Publication year - 2018
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.2995
Subject(s) - enos , medicine , endocrinology , endothelial dysfunction , streptozotocin , diabetes mellitus , endothelial stem cell , nitric oxide , nitric oxide synthase , chemistry , biochemistry , in vitro
Background Diabetes 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. 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 endothelial cell eNOS and CAV‐1 protein expressions were measured. Results Elevated serum Ox‐LDL (STZ 1486 ± 78.1 pg/mL vs control 732.6 ± 160.6 pg/mL, P < .05) was associated with hyperglycaemia (STZ 29 ± 0.9 mmol/L vs control: 7.2 ± 0.2 mmol/L, P < .001) and hypertriglyceridaemia (STZ 9.0 ± 1.5 mmol/L vs control: 3.0 ± 0.3 mmol/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). 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.