Endothelial TFEB (Transcription Factor EB) Positively Regulates Postischemic Angiogenesis

Circulation Research
Yanbo FanY Eugene Chen

Abstract

Postischemic angiogenesis is critical to limit the ischemic tissue damage and improve the blood flow recovery. The regulation and the underlying molecular mechanisms of postischemic angiogenesis are not fully unraveled. TFEB (transcription factor EB) is emerging as a master gene for autophagy and lysosome biogenesis. However, the role of TFEB in vascular disease is less understood. We aimed to determine the role of endothelial TFEB in postischemic angiogenesis and its underlying molecular mechanism. In primary human endothelial cells (ECs), serum starvation induced TFEB nuclear translocation. VEGF (vascular endothelial growth factor) increased TFEB expression level and nuclear translocation. Utilizing genetically engineered EC-specific TFEB transgenic and KO (knockout) mice, we investigated the role of TFEB in postischemic angiogenesis in the mouse hindlimb ischemia model. We observed improved blood perfusion and increased capillary density in the EC-specific TFEB transgenic mice compared with the wild-type littermates. Furthermore, blood flow recovery was attenuated in EC-TFEB KO mice compared with control mice. In aortic ring cultures, the TFEB transgene significantly increased vessel sprouting, whereas TFEB deficiency impair...Continue Reading

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Citations

Jan 4, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Wenying LiangY Eugene Chen
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