Inhibition of the lncRNA Mirt1 Attenuates Acute Myocardial Infarction by Suppressing NF-κB Activation

Abstract

Background/Aims: The expression of a novel lncRNA, myocardial infarction associated transcript 1(Mirt1), has been shown to be upregulated in acute myocardial infarction (AMI). However, the role of Mirt1 in AMI is not clear. Methods: In this study, we analyzed the level of Mirt1 in cardiomyocytes and cardiac fibroblasts in AMI mice. Moreover, adenovirus mediated knockdown of Mirt1 was employed to clarify its roles in AMI mice or cultured cardiac fibroblasts. The cardiac functions and infarct size of AMI mice were examined, and tissues and cultured cells were collected and processed for histology and biochemical examination. Results: We demonstrated that Mirt1 was mainly expressed in cardiac fibroblasts, and that knockdown of Mirt1 improved cardiac functions, decreased cardiomyocytes apoptosis and attenuated inflammatory cell infiltration in vivo. Furthermore, knockdown of Mirt1 in cardiac fibroblasts not only attenuated the apoptosis of cardiomyocytes, but also suppressed the migration of macrophages under hypoxia in vitro. NF-κB signaling pathway, activated under hypoxia, was also inhibited by Mirt1 knockdown in fibroblasts. Conclusions: Knockdown of Mirt1 attenuates AMI injury presumably by decreasing cardiomyocytes apoptosis and reducing inflammatory cell infiltration. These effects could be attributed, at least partly, to inhibition of the NF-κB pathway, resulting in decreased expression of inflammatory factors.

Long non-coding RNA DANCR alleviates hypoxia-caused H9c2 cells damage through up regulation of HIF-1α

“…At present, lncRNA has been found to be irreplaceable in other diseases besides its role in the pathophysiology of cancer, such as ischaemic heart disease (containing myocardial infarction and angina pectoris) [8,9]. For example, Li X et al detected that lncRNA myocardial infarction related transcript 1(Mirt1) was highly expressed in cardiac fibroblasts, and Mirt1 knockdown elevated cardiac roles, reduced cardiomyocytes apoptosis and infiltration of inflammatory cells [10]. Besides that, Gong LC et al demonstrated that hypoxia induced overexpression of lncRNA H19 and H19 knockdown aggravated hypoxia-caused damage presented as raising cell activity, migration and incursion but reducing cell apoptosis via miR-139-mediated positive regulation of Sox8 [11].…”

Targeting MIAT reduces apoptosis of cardiomyocytes after ischemia/reperfusion injury

“…It has recently found that MIAT is upregulated in hearts of a mouse model of AMI, and knocking it down improves cardiac function by inhibition of activation of NF-κB signaling pathway [10]. Furthermore, knockdown of MIAT improved cardiac functions, decreased cardiomyocytes apoptosis and attenuated inflammatory cell infiltration in vivo [11]. However, the underlying mechanisms remains unclear.…”

Overexpression of lncRNA Gm2691 attenuates apoptosis and inflammatory response after myocardial infarction through PI3K/Akt signaling pathway

“…Recently, numerous researchers have paid their attention to lncRNA and other non coding RNA . Hundreds of lncRNAs have been revealed that served an important role in different diseases.…”

“…Recently, numerous researchers have paid their attention to lncRNA and other non coding RNA. 21,24 Hundreds of lncRNAs have been revealed that served an important role in different diseases. LncRNA has a variety of functions, specifically, influencing apoptosis, 24 cell cycle, 25 differenation, 26 regeneration, 27 and migration.…”