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.
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.
objective:
None
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.