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

Diabetes Metab Res Rev. 2018 Jul;34(5):e2995. doi: 10.1002/dmrr.2995. Epub 2018 Mar 15.

Abstract

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.

Keywords: caveolin-1; diabetes; endothelial dysfunction; endothelial nitric oxide synthase; oxidative LDL.

MeSH terms

  • Animals
  • Caveolin 1 / metabolism*
  • Diabetes Mellitus, Experimental / physiopathology*
  • Dyslipidemias / physiopathology*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology*
  • Hyperglycemia / metabolism
  • Hyperglycemia / pathology*
  • Male
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / metabolism*
  • Oxidative Stress
  • Rats
  • Rats, Wistar
  • Vascular Diseases / metabolism
  • Vascular Diseases / pathology*

Substances

  • Cav1 protein, rat
  • Caveolin 1
  • Nitric Oxide
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat