title: MiR-145-5p regulates hypoxia-induced inflammatory response and apoptosis in cardiomyocytes by targeting CD40.
abstract: An increasing body of evidence indicates that inflammation and apoptosis are involved in the development of acute myocardial infarction (AMI). In this study, we sought to investigate the specific role and the underlying regulatory mechanism of miR-145-5p in myocardial ischemic injury. H9c2 cardiac cells were exposed to hypoxia to establish a model of myocardial hypoxic/ischemic injury. We found that miR-145-5p was notably down-regulated, while CD40 expression was highly elevated in H9c2 cells following exposure to acute hypoxia. Additionally, hypoxia markedly enhanced the inflammatory response, as reflected by an increase in the secretion of the cytokines IL-1β, TNF-α, and IL-6, whereas the introduction of miR-145-5p effectively suppressed inflammatory factor production triggered by hypoxia. Furthermore, we observed hypoxia stimulation significantly augmented apoptosis accompanied by a decrease in the expression of Bcl-2 and an increase in the expression of Bax, Caspase-3, and Caspase-9. However, augmentation of miR-145-5p led to a dramatic prevention of hypoxia-induced apoptosis. Importantly, we identified CD40 as a direct target of miR-145-5p. Interestingly, the depletion of CD40 with small interfering RNAs (siRNAs) apparently repressed the production of inflammatory cytokines and apoptosis in the setting of acute hypoxic treated. Taken together, these data demonstrated that miR-145-5p may function as a cardiac-protective molecule in myocardial ischemic injury by ameliorating inflammation and apoptosis via negative regulation of CD40. The study gives evidence that miR-145-5p provides an interesting strategy for protecting cardiomyocytes from hypoxia-induced inflammatory response and apoptosis.
authors.affiliation: Department of Cardiology, Xijing Hospital, Changle Xi 17, Xi'an, 710032, Shaanxi, People's Republic of China. 1446534236@qq.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Yuan
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of General Hospital of PLA, Beijing, 100048, People's Republic of China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Xi'an Central Hospital, Xi'an, 710004, Shaanxi, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: You
authors.affiliation: Department of Cardiology, Xijing Hospital, Changle Xi 17, Xi'an, 710032, Shaanxi, People's Republic of China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of General Hospital of PLA, Beijing, 100048, People's Republic of China.
authors.forename: Yongjiang
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of General Hospital of PLA, Beijing, 100048, People's Republic of China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Xijing Hospital, Changle Xi 17, Xi'an, 710032, Shaanxi, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Tao
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism*; D015687:Cell Hypoxia; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology
chemical_list: D051017:Apoptosis Regulatory Proteins; D019013:CD40 Antigens; D016207:Cytokines; C541010:MIRN145 microRNA, human; D035683:MicroRNAs
keywords: Acute myocardial infarction (AMI); Apoptosis; CD40; Inflammatory response; MiR-145-5p