High glucose induces the apoptosis of HUVECs in mitochondria dependent manner by enhancing VDAC1 expression.

: Mellithemia are diabetic patients' emblematic syndrome, which would induce vasculopathy resulting from apoptosis of vascular endothelial cells. The pathological mechanism of high glucose-induced apoptosis of vascular endothelial cells is investigated in the present study utilizing HUVEC cells. As high glucose-induced apoptosis is caused by elevated mitochondrial permeability-mediated release of mitochondrial cytochrome c, voltage-dependent anion channel (VDAC1), the controller of mitochondrial permeability, and its regulator Bax were investigated. Our results suggest that upregulation of VDAC1 is the central event in high glucose-induced cell apoptosis, since silencing VDAC1 reduced high glucose-induced upregulation of mitochondrial/cellular Bax; thus silencing VDAC1 recovered the high glucose-reduced binding of Bax to VDAC1, which finally reduced the high mitochondrial permeability. Besides, high glucose increased VDAC1 expression by elevating the expression of SREBP1 and SREBP2, the tanscriptional factor of VDAC1. Those findings indicate that SREBP1 or SREBP2/VDAC1 could be novel targets for the prevention of diabetic vasculopathy.