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

• Published in: Cellular physiology and biochemistry Vol. 42; no. 3; pp. 1153 - 1164
• Main Authors: Li, Xiangrao, Zhou, Jian, Huang, Kai
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Cell Physiol Biochem Press GmbH & Co KG 01.01.2017
• Subjects: Acute myocardial infarction; Animals; Cardiomyocyte apoptosis; Disease Models, Animal; Fibroblasts - immunology; Fibroblasts - metabolism; Fibroblasts - pathology; Gene Expression Regulation; Inflammation; Inflammation - genetics; Inflammation - immunology; Inflammation - pathology; Inflammation - therapy; Long noncoding RNA Mirt1; Male; Mice, Inbred C57BL; Myocardial Infarction - genetics; Myocardial Infarction - immunology; Myocardial Infarction - pathology; Myocardial Infarction - therapy; Myocardium - metabolism; Myocardium - pathology; Myocytes, Cardiac - immunology; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; NF-kappa B - immunology; NF-κB; Original Paper; RNA, Long Noncoding - analysis; RNA, Long Noncoding - genetics; RNA, Long Noncoding - immunology; RNA, Small Interfering - genetics; RNAi Therapeutics; NF-κB; Long noncoding RNA Mirt1; Inflammation; Cardiomyocyte apoptosis; Acute myocardial infarction
• ISSN: 1015-8987; 1421-9778; 1421-9778
• DOI: 10.1159/000478870

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.