Long Noncoding RNAs in Myocardial Ischemia-Reperfusion Injury

Following an acute myocardial infarction, reperfusion therapy is currently the most effective way to save the ischemic myocardium; however, restoring blood flow may lead to a myocardial ischemia-reperfusion injury (MIRI). Recent studies have confirmed that long-chain noncoding RNAs (LncRNAs) play important roles in the pathophysiology of MIRIs. These LncRNA-mediated roles include cardiomyocyte apoptosis, autophagy, necrosis, oxidative stress, inflammation, mitochondrial dysfunction, and calcium overload, which are regulated through the expression of target genes. Thus, LncRNAs may be used as clinical diagnostic markers and therapeutic targets to treat or prevent MIRI. This review evaluates the research on LncRNAs involved in MIRIs and provides new ideas for preventing and treating this type of injury.

Download Full-text

Insight into long noncoding RNA–miRNA–mRNA axes in myocardial ischemia-reperfusion injury: the implications for mechanism and therapy

Epigenomics ◽

10.2217/epi-2019-0119 ◽

2019 ◽

Vol 11 (15) ◽

pp. 1733-1748 ◽

Cited By ~ 1

Author(s):

Wei Xiong ◽

Yan Qu ◽

Hongmei Chen ◽

Jinqiao Qian

Keyword(s):

Myocardial Ischemia ◽

Reperfusion Injury ◽

Noncoding Rna ◽

Molecular Mechanisms ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Noncoding Rnas ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion ◽

Insight Into

Emerging evidence has demonstrated that regulatory noncoding RNAs (ncRNAs), such as long noncoding RNAs (lncRNAs) and miRNAs, play crucial roles in the initiation and progress of myocardial ischemia-reperfusion injury (MIRI), which is associated with autophagy, apoptosis and necrosis of cardiomyocytes, as well as oxidative stress, inflammation and mitochondrial dysfunction. LncRNAs serve as a precursor or host of miRNAs and directly/indirectly affecting miRNAs via competitive binding or sponge effects. Simultaneously, miRNAs post-transcriptionally regulate the expression of genes by targeting various mRNA sequences due to their imperfect pairing with mRNAs. This review summarizes the potential regulatory role of lncRNA–miRNA–mRNA axes in MIRI and related molecular mechanisms of cardiac disorders, also provides insight into the potential therapies for MIRI-induced diseases.

Download Full-text

Roles of noncoding RNAs in the initiation and progression of myocardial ischemia reperfusion injury

Epigenomics ◽

10.2217/epi-2020-0359 ◽

2021 ◽

Author(s):

Xiang-feng Bai ◽

Rui-ze Niu ◽

Jia Liu ◽

Xu-dong Pan ◽

Feng Wang ◽

...

Keyword(s):

Myocardial Ischemia ◽

Reperfusion Injury ◽

Bioinformatics Analysis ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Noncoding Rnas ◽

Modern Society ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion ◽

Preclinical And Clinical Studies

The morbidity and mortality of myocardial ischemia reperfusion injury (MIRI) have increased in modern society. Noncoding RNAs (ncRNAs), including lncRNAs, circRNAs, piRNAs and miRNAs, have been reported in a variety of studies to be involved in pathological initiation and developments of MIRI. Hence this review focuses on the current research regarding these ncRNAs in MIRI. We comprehensively introduce the important features of lncRNAs, circRNAs, piRNA and miRNAs and then summarize the published studies of ncRNAs in MIRI. A clarification of lncRNA–miRNA–mRNA, lncRNA–transcription factor–mRNA and circRNA–miRNA–mRNA axes in MIRI follows, to further elucidate the crucial roles of ncRNAs in MIRI. Bioinformatics analysis has revealed the biological correlation of mRNAs with MIRI. We provide a comprehensive perspective for the roles of these ncRNAs and their related networks in MIRI, providing a theoretical basis for preclinical and clinical studies on ncRNA-based gene therapy for MIRI treatment.

Download Full-text

Up-regulation of CTRP12 ameliorates hypoxia/re-oxygenation-induced cardiomyocyte injury by inhibiting apoptosis, oxidative stress, and inflammation via the enhancement of Nrf2 signaling

Human & Experimental Toxicology ◽

10.1177/09603271211021880 ◽

2021 ◽

pp. 096032712110218

Author(s):

Ai-Ping Jin ◽

Qian-Rong Zhang ◽

Cui-Ling Yang ◽

Sha Ye ◽

Hai-Juan Cheng ◽

...

Keyword(s):

Oxidative Stress ◽

Myocardial Ischemia ◽

Reperfusion Injury ◽

Target Genes ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Myocardial Ischemia Reperfusion Injury ◽

Artery Disease ◽

Myocardial Ischemia Reperfusion

C1q/TNF-related protein 12 (CTRP12) has been reported to play a key role in coronary artery disease. However, whether CTRP12 plays a role in the regulation of myocardial ischemia-reperfusion injury is not fully understood. The goals of this work were to assess the possible relationship between CTRP12 and myocardial ischemia-reperfusion injury. Here, we exposed cardiomyocytes to hypoxia/re-oxygenation (H/R) to establish an in vitro cardiomyocyte injury model of myocardial ischemia-reperfusion injury. Our results showed that H/R treatment resulted in a decrease in CTRP12 expression in cardiomyocytes. The up-regulation of CTRP12 ameliorated H/R-induced cardiomyocyte injury via the down-regulation of apoptosis, oxidative stress, and inflammation. In contrast, the knockdown of CTRP12 enhanced cardiomyocyte sensitivity to H/R-induced cardiomyocyte injury. Further investigation showed that CTRP12 enhanced the levels of nuclear Nrf2 and increased the expression of Nrf2 target genes in cardiomyocytes exposed to H/R. However, the inhibition of Nrf2 markedly diminished CTRP12-overexpression-mediated cardioprotective effects against H/R injury. Overall, these data indicate that CTRP12 protects against H/R-induced cardiomyocyte injury by inhibiting apoptosis, oxidative stress, and inflammation via the enhancement of Nrf2 signaling. This work suggests a potential role of CTRP12 in myocardial ischemia-reperfusion injury and proposes it as an attractive target for cardioprotection.

Download Full-text

LATS2 Deletion Attenuates Myocardial Ischemia-Reperfusion Injury by Promoting Mitochondrial Biogenesis

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/1058872 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Yi Chen ◽

Chen Liu ◽

Jiannan Li ◽

Peng Zhou ◽

Xiaoxiao Zhao ◽

...

Keyword(s):

Myocardial Ischemia ◽

Reperfusion Injury ◽

Mitochondrial Biogenesis ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Reperfusion Therapy ◽

Large Tumor ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

Reperfusion therapy is the most effective treatment for acute myocardial infarction, but it can damage cardiomyocytes through a mechanism known as myocardial ischemia/reperfusion injury (MIRI). In this study, we investigated whether the large tumor suppressor kinase 2 (LATS2) contributes to the development of myocardial MIRI by disrupting mitochondrial biogenesis. Our in vitro data demonstrate that cardiomyocyte viability was reduced and apoptosis was increased in response to hypoxia/reoxygenation (H/R) injury. However, suppression of LATS2 by shRNA sustained cardiomyocyte viability by maintaining mitochondrial function. Compared to H/R-treated control cardiomyocytes, cardiomyocytes transfected with LATS2 shRNA exhibited increased mitochondrial respiration, improved mitochondrial ATP generation, and more stable mitochondrial membrane potential. LATS2 suppression increased cardiomyocyte viability and mitochondrial biogenesis in a manner dependent on PGC1α, a key regulator of mitochondrial metabolism. These results identify LATS2 as a new inducer of mitochondrial damage and myocardial MIRI and suggest that approaches targeting LATS2 or mitochondrial biogenesis may be beneficial in the clinical management of cardiac MIRI.

Download Full-text

miRNA-27a Transcription Activated by c-Fos Regulates Myocardial Ischemia-Reperfusion Injury by Targeting ATAD3a

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/2514947 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Yandong Bao ◽

Ying Qiao ◽

Hang Yu ◽

Zeying Zhang ◽

Huimin Yang ◽

...

Keyword(s):

Myocardial Ischemia ◽

Reperfusion Injury ◽

Target Genes ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Isolated Rat Heart ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

MicroRNA-27a (miR-27a) has been implicated in myocardial ischemia-reperfusion injury (MIRI), but the underlying mechanism is not well understood. This study is aimed at determining the role of miR-27a in MIRI and at investigating upstream molecules that regulate miR-27a expression and its downstream target genes. miR-27a expression was significantly upregulated in myocardia exposed to ischemia/reperfusion (I/R) and cardiomyocytes exposed to hypoxia/reoxygenation (H/R). c-Fos could regulate miR-27a expression by binding to its promoter region. Moreover, overexpression of miR-27a led to a decrease in cell viability, an increase in LDH and CK-MB secretion, and an increase in apoptosis rates. In contrast, suppression of miR-27a expression resulted in the opposite effects. ATPase family AAA-domain-containing protein 3A (ATAD3a) was identified as a target of miR-27a. miR-27a regulated the translocation of apoptosis-inducing factor (AIF) from the mitochondria to the nucleus and H/R-induced apoptosis via the regulation of ATAD3a. It was found that inhibiting miR-27a in vivo by injecting a miR-27a sponge could ameliorate MIRI in an isolated rat heart model. In conclusion, our study demonstrated that c-Fos functions as an upstream regulator of miR-27a and that miR-27a regulates the translocation of AIF from the mitochondria to the nucleus by targeting ATAD3a, thereby contributing to MIRI. These findings provide new insight into the role of the c-Fos/miR-27a/ATAD3a axis in MIRI.

Download Full-text