HIF-1α Contributes to Hypoxia-induced VSMC Proliferation and Migration by Regulating Autophagy in Type A Aortic Dissection.

Abstract

Type A aortic dissection (AD) is a catastrophic cardiovascular disease. Hypoxia-inducible factor-1α (HIF-1α) and autophagy are reported to be upregulated in the AD specimens. However, the interaction between HIF-1α and autophagy in the pathogenesis of AD remains to be explored. HIF-1α and LC3 levels are evaluated in 10 AD and 10 normal aortic specimens. MDC staining, autophagic vacuoles, and autophagic flux are detected in human aortic smooth muscle cells (HASMCs) under hypoxia treatment. CCK-8, transwell, and wound healing assay are used to identify proliferation and migration under hypoxia treatment. Furthermore, 3-MA is used to inhibit autophagy in hypoxia-treated HASMCs. This study reveals that AD tissues highly express HIF-1α and the LC3. Autophagy is induced under hypoxia in a time-dependent manner, and autophagy is positively related to HIF-1α in HASMCs. Moreover, the proliferation and migration of HASMCs are enhanced by hypoxia, whereas the knockdown of HIF-1α attenuates this effect. Additionally, inhibiting autophagy with 3-MA ameliorates hypoxia-induced proliferation and migration of HASMCs. In summary, the above results indicate that HIF-1α facilitates HASMC proliferation and migration by upregulating autophagy in a hypoxic microenvironment. Thus, inhibition of autophagy may be a novel therapeutic target for the prevention and treatment of AD.