Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China.
Sleep Breath. 2021 Dec;25(4):2241-2250. doi: 10.1007/s11325-021-02319-x. Epub 2021 Mar 10.
Increasing medical researche shows that endothelial dysfunction is one of the important causes of various cardiovascular diseases related to chronic intermittent hypoxia (CIH). This study aimed to identify target proteins in CIH-related vascular dysfunction.
A comparative proteomics analysis was conducted in aortic samples of rats treated with CIH and controls with normoxia. Bioinformatics analyses were performed to determine the potential roles of major proteins. The expressions of target proteins were measured by western blotting. Cell apoptotic ratio was detected by flow cytometer.
A total of 3,593 proteins in aortic tissues of rats were quantified. Ninety-two upregulated proteins and 468 downregulated proteins were identified when the cutoff of fold change was set at 1.5 (CIH vs. normoxia). The results of bioinformatics analysis revealed that the differentially expressed proteins were enriched in the processes of energy metabolism and lipid metabolism. The reduced expression level of peroxisome proliferator-activated receptor γ (PPARγ) protein was identified in thoracic aortic tissues of rats with CIH by proteomics analysis and western blotting. In intermittent hypoxia-treated rat aortic endothelial cells, PPARγ protein levels were reduced, and the apoptosis rate and caspase-3 and Bax protein levels were markedly elevated. Importantly, forced expression of PPARγ by rosiglitazone in intermittent hypoxia-treated rat aortic endothelial cells not only attenuated caspase-3 and Bax protein levels but also reduced the rate of apoptosis.
PPARγ is critical in endothelial dysfunction of rats with CIH. Additional studies on these differentially expressed proteins associated with CIH-related endothelial dysfunction are necessary.
越来越多的医学研究表明，内皮功能障碍是与慢性间歇性低氧（CIH）相关的各种心血管疾病的重要原因之一。本研究旨在确定与 CIH 相关血管功能障碍相关的靶蛋白。
对慢性间歇性低氧和常氧对照组大鼠主动脉样本进行比较蛋白质组学分析。通过生物信息学分析确定主要蛋白质的潜在作用。通过 Western blot 测定靶蛋白的表达。通过流式细胞仪检测细胞凋亡率。
定量了大鼠主动脉组织中的 3593 种蛋白质。当倍数变化的截止值设置为 1.5（CIH 与常氧相比）时，鉴定出 92 个上调蛋白和 468 个下调蛋白。生物信息学分析的结果表明，差异表达蛋白富集在能量代谢和脂质代谢过程中。通过蛋白质组学分析和 Western blot 鉴定，发现 CIH 大鼠胸主动脉组织中过氧化物酶体增殖物激活受体γ（PPARγ）蛋白表达降低。在间歇性低氧处理的大鼠主动脉内皮细胞中，PPARγ 蛋白水平降低，细胞凋亡率和 caspase-3 和 Bax 蛋白水平明显升高。重要的是，用罗格列酮在间歇性低氧处理的大鼠主动脉内皮细胞中强制表达 PPARγ，不仅降低了 caspase-3 和 Bax 蛋白水平，而且降低了细胞凋亡率。
PPARγ 在 CIH 大鼠的内皮功能障碍中起关键作用。需要对与 CIH 相关的内皮功能障碍相关的这些差异表达蛋白进行进一步研究。
