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Verification of ferroptosis and pyroptosis and identification of PTGS2 as the hub gene in human coronary artery atherosclerosis
Free Radical Biology and Medicine ( IF 7.1 ) Pub Date : 2021-05-08 , DOI: 10.1016/j.freeradbiomed.2021.05.009
Yaqing Zhou 1 , Hanxiao Zhou 1 , Lei Hua 1 , Can Hou 1 , Qiaowei Jia 1 , Jiaxin Chen 1 , Sheng Zhang 1 , Yanjun Wang 1 , Shu He 1 , Enzhi Jia 1
Affiliation  

Ferroptosis and pyroptosis have not been fully studied in atherosclerosis. We aimed to investigate the expression of ferroptosis-related and pyroptosis-related proteins in human coronary arteries and analyse correlation with severity of atherosclerosis and clarify the interactions between proteins and possible mechanisms of atherosclerosis. 40 human coronary artery specimens were employed. The atherosclerotic lesions were characterized by Haematoxylin and Eosin (H&E) staining. The expression of prostaglandin-endoperoxide synthase 2 (PTGS2), anti-acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), caspase-1, and NOD-like receptor protein 3 (NLRP3) were analysed by immunohistochemical assay. Correlations between expression of proteins and severity of atherosclerosis were assessed using Spearman correlation analysis. Bioinformatic and coexpression analyses were performed to study the possible pathways and interactions. In the present study, PTGS2, ACSL4, caspase-1, and NLRP3, were upregulated, while GPX4 was downregulated in the advanced stages of atherosclerosis. The severity of atherosclerosis was positively associated with the expression of PTGS2, ACSL4, caspase-1, and NLRP3 and negatively associated with the expression of GPX4. Biological processes of lipid metabolism and inflammation and C-type lectin receptor signaling pathway were enriched. The five proteins interacted with each other directly or indirectly and PTGS2 might be the hub gene of atherosclerosis. Ferroptosis and pyroptosis may regulate the occurrence and development of atherosclerosis. These findings may shed light on new ideas and potential targets for the prevention and treatment of coronary artery atherosclerosis and the proteins may be used as biomarkers for the severity of atherosclerosis.



中文翻译:

铁死亡和焦亡的验证及PTGS2作为人类冠状动脉粥样硬化中枢基因的鉴定

铁死亡和焦亡尚未在动脉粥样硬化中得到充分研究。我们旨在研究人冠状动脉中铁死亡相关和焦亡相关蛋白的表达,分析与动脉粥样硬化严重程度的相关性,阐明蛋白质之间的相互作用和动脉粥样硬化的可能机制。使用了 40 个人类冠状动脉标本。动脉粥样硬化病变的特点是苏木精和伊红 (H&E) 染色。前列腺素内过氧化物合酶 2 (PTGS2)、抗酰基辅酶 A 合成酶长链家族成员 4 (ACSL4)、谷胱甘肽过氧化物酶 4 (GPX4)、caspase-1 和 NOD 样受体蛋白 3 (NLRP3) 的表达分别为通过免疫组织化学分析进行分析。使用Spearman相关分析评估蛋白质表达与动脉粥样硬化严重程度之间的相关性。进行生物信息学和共表达分析以研究可能的途径和相互作用。在本研究中,在动脉粥样硬化的晚期阶段,PTGS2、ACSL4、caspase-1 和 NLRP3 上调,而 GPX4 下调。动脉粥样硬化的严重程度与PTGS2、ACSL4、caspase-1和NLRP3的表达呈正相关,与GPX4的表达呈负相关。丰富了脂质代谢和炎症的生物学过程以及C型凝集素受体信号通路。这五种蛋白质直接或间接相互作用,PTGS2可能是动脉粥样硬化的中枢基因。铁死亡和焦亡可能调节动脉粥样硬化的发生和发展。这些发现可能为预防和治疗冠状动脉粥样硬化提供新思路和潜在靶点,并且这些蛋白质可用作动脉粥样硬化严重程度的生物标志物。

更新日期:2021-05-14
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