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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Research Article

Rosuvastatin Improves Endothelial Dysfunction in Diabetes by Normalizing Endoplasmic Reticulum Stress via Calpain-1 Inhibition

Author(s): Zhao Zhao, Xinpeng Wang, Meili Lu* and Yuxia Gao*

Volume 29, Issue 32, 2023

Published on: 20 October, 2023

Page: [2579 - 2590] Pages: 12

DOI: 10.2174/0113816128250494231016065438

Price: $65

Abstract

Background: Rosuvastatin contributes to the improvement of vascular complications in diabetes, but the protective mechanisms remain unclear. The aim of the present study was to investigate the effect and mechanism of rosuvastatin on endothelial dysfunction induced by diabetes.

Methods: Calpain-1 knockout (Capn1 EK684-/-) and C57BL/6 mice were intraperitoneally injected with STZ to induce type 1 diabetes. Human umbilical vein endothelial cells (HUVECs) were incubated with high glucose in this study. The function of isolated vascular rings, apoptosis, and endoplasmic reticulum stress (ERS) indicators were measured in this experiment.

Results: The results showed that rosuvastatin (5 mg/kg/d) and calpain-1 knockout improved impaired vasodilation in an endothelial-dependent manner, and this effect was abolished by an ERS inducer. Rosuvastatin administration inhibited calpain-1 activation and ERS induced by high glucose, as well as apoptosis and oxidative stress both in vivo and in vitro. In addition, an ERS inducer (tunicamycin) offset the beneficial effect of rosuvastatin on endothelial dysfunction and ERS, which was accompanied by increased calpain-1 expression. The ERS inhibitor showed a similar improvement in endothelial dysfunction with rosuvastatin but could not increase the improvement in endothelial function of rosuvastatin.

Conclusion: These results suggested that rosuvastatin improves endothelial dysfunction by suppressing calpain- 1 and normalizing ERS, subsequently decreasing apoptosis and oxidative stress.

Keywords: Rosuvastatin, endoplasmic reticulum stress, calpain-1, endothelial dysfunction, apoptosis, oxidative stress.

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