Connexin43 overexpression promoted ferroptosis and increased myocardial vulnerability to ischemia-reperfusion injury in type 1 diabetic mice

doi:10.7150/ijms.95170

科研成果详情

题名	Connexin43 overexpression promoted ferroptosis and increased myocardial vulnerability to ischemia-reperfusion injury in type 1 diabetic mice
作者	Yuhui Yang 1; Jiajia Chen 1; Jiaqi Zhou 1; Dongcheng Zhou 1; Anyuan Zhang2; Yuxin Jiang 1; Jiefu Lin 1; Weiyi Xia 1,3; Yin Cai 3; Ronghui Han 1; Yan Lu 1; Danyong Liu 1; Zhengyuan Xia 1,4
发表日期	2024
发表期刊	International journal of medical sciences 影响因子和分区
语种	英语
原始文献类型	Journal Article
摘要	Enhancement of Connexin43 (Cx43) and ferroptosis are respectively associated with the exacerbation of myocardial ischemia-reperfusion injury (MIRI) in diabetes. Myocardial vulnerability to ischemic insult has been shown to vary during early and later phases of diabetes in experimental settings. Whether or not Connexin43 (Cx43) and ferroptosis interplay during MIRI in diabetes is unknown. We, thus, aimed to investigate whether or not the content of myocardial Cx43 may be attributable to myocardial vulnerability to MIRI at different stages of diabetes and also to explore the potential interplay between Cx43 and ferroptosis in this pathology. Age-matched control and subgroups of Streptozotocin-induced diabetic mice were subjected to MIRI induced by 30 minutes coronary artery occlusion and 2 hours reperfusion respectively at 1, 2 and 5 weeks of diabetes. Rat cardiac H9C2 cells were exposed to high glucose (HG) for 48h in the absence or presence of Cx43 gene knockdown followed by hypoxia/reoxygenation (HR) respectively for 6 and 12 hours. Post-ischemic myocardial infarct size was reduced in 1 and 2 weeks DM mice concomitant with enhanced GPX4 and reduced cardiac Cx43 and ferroptosis as compared to control. By contrast, cardiac GPX4 was significantly reduced while Cx43 increased at DM 5 weeks (D5w) which was correspondent to significant increases in ferroptosis and myocardial infarction. Post-ischemic cardiac function was improved in 1 and 2 weeks but worsened in 5w DM mice as compared with non-diabetic control. GAP19 (Cx43 inhibitor) significantly attenuated ferroptosis and reduced myocardial infarction in D5w mice. Erastin (ferroptosis activator) reversed the cardioprotective effect of GAP19. In vitro, HR significantly reduced cell viability accompanied with reduced GPX4 but elevated Cx43 expression, MDA production and ferroptosis. Cx43 gene knockdown in H9C2 resulted in a significant increase in GPX4, reduction in MDA and ferroptosis, and subsequently reduced post-hypoxic cell viability. The beneficial effects of Cx43 gene knock-down was minified or eliminated by Erastin. It is concluded that Cx43 overexpression exacerbates MIRI under diabetic conditions via promoting ferroptosis, while its down-regulation at early state of diabetes is attributable to enhanced myocardial tolerance to MIRI.
ISSN	1449-1907
卷号	21 期号:12
DOI	10.7150/ijms.95170
收录类别	PUBMED
URL	查看原文
PubMed ID	39310260
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/218941
专题	第二临床医学院，附属第二医院、育英儿童医院_麻醉学_麻醉科
作者单位	1.Department of Anesthesiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524000, China.; 2.Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, 325027, China.; 3.Department of Health Technology and Informatics, the Hong Kong Polytechnic University, Hong Kong, China.; 4.Doctoral Training Platform for Research and Translation, BoShiWan, ZhongXiang City, Hubei, 431900, China.
推荐引用方式 GB/T 7714	Yuhui Yang,Jiajia Chen,Jiaqi Zhou,et al. Connexin43 overexpression promoted ferroptosis and increased myocardial vulnerability to ischemia-reperfusion injury in type 1 diabetic mice[J]. International journal of medical sciences,2024,21(12).
APA	Yuhui Yang., Jiajia Chen., Jiaqi Zhou., Dongcheng Zhou., Anyuan Zhang., ... & Zhengyuan Xia. (2024). Connexin43 overexpression promoted ferroptosis and increased myocardial vulnerability to ischemia-reperfusion injury in type 1 diabetic mice. International journal of medical sciences, 21(12).
MLA	Yuhui Yang,et al."Connexin43 overexpression promoted ferroptosis and increased myocardial vulnerability to ischemia-reperfusion injury in type 1 diabetic mice".International journal of medical sciences 21.12(2024).