Ningfang Lian1, Mengxue Chen1, Shuyi Zhang1, Lida Chen1, Jiefeng Huang1, Qichang Lin2. 1. Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China. 2. Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China. linqc_fy@126.com.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Wassim W Labaki; Lucas M Kimmig; Gökhan M Mutlu; MeiLan K Han; Surya P Bhatt Journal: Am J Respir Crit Care Med Date: 2019-06-15 Impact factor: 21.405
Authors: Md Sahab Uddin; Md Tanvir Kabir; Md Jakaria; Abdullah Al Mamun; Kamal Niaz; Md Shah Amran; George E Barreto; Ghulam Md Ashraf Journal: Neurotox Res Date: 2019-05-04 Impact factor: 3.911