Huang Ben, Chen Nan, Chen Zhenhang, Shen Jinqiang, Zhang Hao, Wang Chunsheng, Sun Yongxin
Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, P.R. China.
Adv Biol (Weinh). 2024 Jan;8(1):e2300292. doi: 10.1002/adbi.202300292. Epub 2023 Oct 2.
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.
A型主动脉夹层（AD）是一种灾难性的心血管疾病。据报道，缺氧诱导因子-1α（HIF-1α）和自噬在AD标本中上调。然而，HIF-1α与自噬在AD发病机制中的相互作用仍有待探索。在10个AD主动脉标本和10个正常主动脉标本中评估HIF-1α和LC3水平。在缺氧处理的人主动脉平滑肌细胞（HASMCs）中检测单丹磺酰尸胺（MDC）染色、自噬泡和自噬通量。采用CCK-8、Transwell和伤口愈合试验来鉴定缺氧处理下的增殖和迁移情况。此外，使用3-甲基腺嘌呤（3-MA）抑制缺氧处理的HASMCs中的自噬。本研究表明，AD组织中HIF-1α和LC3高度表达。缺氧条件下自噬呈时间依赖性诱导，且在HASMCs中自噬与HIF-1α呈正相关。此外，缺氧增强了HASMCs的增殖和迁移，而敲低HIF-1α可减弱这种作用。另外，用3-MA抑制自噬可改善缺氧诱导的HASMCs增殖和迁移。总之，上述结果表明，在缺氧微环境中，HIF-1α通过上调自噬促进HASMCs增殖和迁移。因此，抑制自噬可能是预防和治疗AD的新治疗靶点。
