Xue-Lian Song1, Fei-Fei Zhang2, Wen-Jing Wang2, Xin-Ning Li2, Yi Dang2, Ying-Xiao Li2, Qian Yang2, Mei-Jing Shi2, Xiao-Yong Qi3,4. 1. Graduate School, Hebei Medical University, Shijiazhuang, 050017, Hebei, People's Republic of China. 2. Department of Cardiology Center, Hebei General Hospital, No. 348 of Heping West Road, Shijiazhuang, 050051, Hebei, People's Republic of China. 3. Graduate School, Hebei Medical University, Shijiazhuang, 050017, Hebei, People's Republic of China. youyouqiu88@126.com. 4. Department of Cardiology Center, Hebei General Hospital, No. 348 of Heping West Road, Shijiazhuang, 050051, Hebei, People's Republic of China. youyouqiu88@126.com.
Abstract
BACKGROUND: Myocardial ischemia and reperfusion injury (MI/RI) is a complex pathophysiological process, which can lead to severe myocardial injury. The long noncoding RNA alpha-2-macroglobulin antisense RNA 1 (A2M-AS1) has been revealed to be abnormally expressed in MI, However, its function in MI and the potential mechanism are still unclear. OBJECTIVE: To evaluate the functional role of A2M-AS1 in hypoxia/reoxygenation (H/R)-induced neonatal cardiomyocytes and its potential molecular mechanism. METHODS: Dataset GSE66360 was obtained from GEO database for analyzing the RNA expression of A2M-AS1 and interleukin 1 receptor type 2 (IL1R2). KEGG pathway enrichment analysis of the genes that co-expressed with A2M-AS1 was performed. Human neonatal cardiomyocytes were subjected to H/R to construct in vitro models. QRT-PCR and Western blot were adopted to test the levels of mRNA and protein. The viability and apoptosis of cardiomyocytes were tested by CCK-8 and flow cytometry assays, respectively. RESULTS: The expression of A2M-AS1 was notably downregulated in H/R-treated cardiomyocytes. Overexpression of A2M-AS1 can notably enhance the cell viability of H/R-damaged cardiomyocytes, whereas knockdown of A2M-AS1 showed the opposite outcomes. Besides, a negative correlation was showed between A2M-AS1 and IL1R2 expression. In H/R-treated cardiomyocytes, overexpression of IL1R2 weakened the promoting proliferation and anti-apoptosis effects caused by overexpressing A2M-AS1, however, IL1R2-knockdown abolished the anti-proliferation and pro-apoptosis effects caused by silencing A2M-AS1. CONCLUSION: This study demonstrates the potential regulatory role of A2M-AS1/ IL1R2 axis in cardiomyocytes suffered from H/R, and provides insight into the protection of MI/RI.
BACKGROUND:Myocardial ischemia and reperfusion injury (MI/RI) is a complex pathophysiological process, which can lead to severe myocardial injury. The long noncoding RNA alpha-2-macroglobulin antisense RNA 1 (A2M-AS1) has been revealed to be abnormally expressed in MI, However, its function in MI and the potential mechanism are still unclear. OBJECTIVE: To evaluate the functional role of A2M-AS1 in hypoxia/reoxygenation (H/R)-induced neonatal cardiomyocytes and its potential molecular mechanism. METHODS: Dataset GSE66360 was obtained from GEO database for analyzing the RNA expression of A2M-AS1 and interleukin 1 receptor type 2 (IL1R2). KEGG pathway enrichment analysis of the genes that co-expressed with A2M-AS1 was performed. Humanneonatal cardiomyocytes were subjected to H/R to construct in vitro models. QRT-PCR and Western blot were adopted to test the levels of mRNA and protein. The viability and apoptosis of cardiomyocytes were tested by CCK-8 and flow cytometry assays, respectively. RESULTS: The expression of A2M-AS1 was notably downregulated in H/R-treated cardiomyocytes. Overexpression of A2M-AS1 can notably enhance the cell viability of H/R-damaged cardiomyocytes, whereas knockdown of A2M-AS1 showed the opposite outcomes. Besides, a negative correlation was showed between A2M-AS1 and IL1R2 expression. In H/R-treated cardiomyocytes, overexpression of IL1R2 weakened the promoting proliferation and anti-apoptosis effects caused by overexpressing A2M-AS1, however, IL1R2-knockdown abolished the anti-proliferation and pro-apoptosis effects caused by silencing A2M-AS1. CONCLUSION: This study demonstrates the potential regulatory role of A2M-AS1/ IL1R2 axis in cardiomyocytes suffered from H/R, and provides insight into the protection of MI/RI.
Entities:
Keywords:
Alpha-2-macroglobulin antisense RNA 1; Apoptosis; Interleukin 1 receptor type 2; Myocardial ischemia and reperfusion injury; Proliferation
Authors: Lea Zillich; Eric Poisel; Fabian Streit; Josef Frank; Gabriel R Fries; Jerome C Foo; Marion M Friske; Lea Sirignano; Anita C Hansson; Markus M Nöthen; Stephanie H Witt; Consuelo Walss-Bass; Rainer Spanagel; Marcella Rietschel Journal: J Pers Med Date: 2022-04-02