Suppression of Long Non-Coding RNA LINC00652 Restores Sevoflurane-Induced Cardioprotection Against Myocardial Ischemia-Reperfusion Injury by Targeting GLP-1R Through the cAMP/PKA Pathway in Mice

Abstract

Background/Aims: Long non-coding RNA (lncRNA) and glucagon-like peptide 1 receptor (GLP-1R) are crucial for heart development and for adult heart structural maintenance and function. Herein, we performed a study to explore the effect of lncRNA LINC00652 (LINC00652) on myocardial ischemia-reperfusion (I/R) injury by targeting GLP-1R through the cyclic adenosine monophosphate-protein kinase A (cAMP/PKA) pathway. Methods: Bioinformatics software was used to screen the long-chain non-coding RNAs associated with myocardial ischemia-reperfusion and to predict target genes. The mRNA and protein levels of LINC00652, GLP-1R and CREB were detected by RT-qPCR and western blotting. In order to identify the interaction between LINC00652 and myocardial I/R injury, the cardiac function, the hemodynamic changes, the pathological changes of the myocardial tissues, the myocardial infarct size, and the apoptosis of myocardial cells of mice were measured. Meanwhile, the levels of serum IL-1β and TNF-α were detected. Results: LINC00652 was overexpressed in the myocardial cells of mice with myocardial I/R injury. GLP-1R is the target gene of LINC00652. We also determined higher levels of LINC00652 and GLP-1R in the I/R modeled mice. Additionally, si-LINC00652 decreased cardiac pathology, infarct size, apoptosis rates of myocardial cells, and levels of IL-1β and TNF-α, and increased GLP-1R expression cardiac function, normal hemodynamic index, and the expression and phosphorylation of GLP-1R and CREB proteins. Conclusion: Taken together, our key findings of the present highlight LINC00652 inhibits the activation of the cAMP/PKA pathway by targeting GLP-1R to reduce the protective effect of sevoflurane on myocardial I/R injury in mice.

Long noncoding RNA NEAT1 sponges miR‐495‐3p to enhance myocardial ischemia‐reperfusion injury via MAPK6 activation

“…For example, lncRNA necrosis‐related factor (NRF) can modulate myocardial injury in the ischemia and reperfusion via sponging miR‐873 (K. Wang et al, ). Repression of lncRNA LINC00652 can rescue the sevoflurane‐triggered cardioprotection to inhibit the M‐I/R by regulating GLP‐1R and cyclic adenosine 3′,5′‐monophosphate/protein kinase A (cAMP/PKA; Zhang et al, ). Cardiac autophagy inhibitory factor (CAIF) can inhibit autophagy process and attenuate the myocardial infarction via preventing p53‐regulated transcription of myocardin (C. Y. Liu et al, ).…”

LncRNA Rik-203 contributes to anesthesia neurotoxicity via microRNA-101a-3p and GSK-3β-mediated neural differentiation

“…LncRNA Gadd45a upregulation is associated with sevoflurane-induced neurotoxicity in rat neural stem cells 58 . LINC00652 reduce the protective effect of sevoflurane on myocardial ischemia-reperfusion injury in mice 59 . These studies suggested the complex regulation of sevoflurane to lncRNAs and indicated the potential different signaling pathway of sevoflurne /LncRNAs axis.…”

Emerging role of non-coding RNAs and extracellular vesicles in cardioprotection by remote ischemic conditioning of the heart

“…In addition to miRNAs, there is increasing evidence about the role of other types of non-coding RNAs, particularly circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) in cardiac function in both health and disease (Bei et al, 2018;Devaux et al, 2015;Devaux, 2017;Hobuß et al, 2019). Recently, it has been shown that changed expression of certain lncRNAs might be associated with cardioprotection against I/R injury (Kong et al, 2019;Zhang et al, 2018); however, there is no information about the particular role of lncRNAs in remote cardioprotection by RIC. Furthermore, upregulation of several circRNAs such as Cdr1as (antisense circRNA to the cerebellar degeneration-related protein 1 transcript) (Geng et al, 2016), MFACR (mitochondrial fission and apoptosis-related circRNA) (Wang et al, 2017), MICRA (myocardial infarction-associated circRNA) (Salgado-Somoza et al, 2017) or circNCX1 (circRNA transcribed from the sodium/calcium exchanger-1 gene) have been shown to participate to cellular injury due to myocardial infarction and to regulate mitochondrial dynamics and apoptosis in the heart.…”