MicroRNA-221 protects myocardial contractility in myocardial ischemia/reperfusion injury through phospholamban.
<h4>Objective</h4>To investigate the effects and mechanisms of miRNA 221 on myocardial ischemia/reperfusion injury (MIRI) in mice through the regulation of phospholamban (PLB) expression.<h4>Methods</h4>The MIRI mouse model was created and mice were divided into sham, MIRI, M...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0316887 |
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| author | Hongyu Li Jimiao Qiu Chang Liu Guobing Yu Danyu Wu Yichun Chu Kai Wang |
| author_facet | Hongyu Li Jimiao Qiu Chang Liu Guobing Yu Danyu Wu Yichun Chu Kai Wang |
| author_sort | Hongyu Li |
| collection | DOAJ |
| description | <h4>Objective</h4>To investigate the effects and mechanisms of miRNA 221 on myocardial ischemia/reperfusion injury (MIRI) in mice through the regulation of phospholamban (PLB) expression.<h4>Methods</h4>The MIRI mouse model was created and mice were divided into sham, MIRI, MIRI+ 221, and MIRI+ scr groups, with miRNA 221 overexpression induced in the myocardium of MIRI mice by targeted myocardial injection. Quantitative RT-PCR analysis was performed to observe the variation in miRNA 221, PLB, SERCA2, RYR2, NCX1, Cyt C and caspase 3 mRNA levels in myocardium, while Western blot assessed the levels of PLB, p-PLB (Ser16), p-PLB (Thr17), SERCA2, RYR2, NCX1, Cyt C and caspase 3 proteins. Changes in the structural integrity of the mouse heart were identified with HE and MASSON staining, while TUNEL staining was used to evaluate the TUNEL-positive cells of cardiomyocytes. Changes in myocardium calcium concentration were detected with reagent kits and the targeting interaction between miRNA 221 and PLB was evaluated using a luciferase reporter assay.<h4>Results</h4>In the myocardium of MIRI mice, miRNA 221 level was significantly reduced, while the levels of PLB, p-PLB (Ser16), p-PLB (Thr17), and apoptosis-related genes caspase 3, and Cyt C were increased markedly, as well as calcium levels in myocardium. Following the overexpression of miRNA 221 in myocardium, there was a marked alleviation of myocardial injury and cardiomyocyte apoptosis and necrosis, significant enhancement of left ventricular systolic function, and marked decrease in the levels of PLB, p-PLB (Ser16), p-PLB (Thr17), caspase 3 and Cyt C, as well as a significant decrease in total calcium levels in myocardium.<h4>Conclusions</h4>miRNA 221 can alleviate myocardial injury in mouse myocardial ischemia/reperfusion by suppressing the expression of PLB, thus reducing calcium overload in myocardium. |
| format | Article |
| id | doaj-art-b0beb1ac627e4285b2d808bfc6966f49 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-b0beb1ac627e4285b2d808bfc6966f492025-02-05T05:31:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031688710.1371/journal.pone.0316887MicroRNA-221 protects myocardial contractility in myocardial ischemia/reperfusion injury through phospholamban.Hongyu LiJimiao QiuChang LiuGuobing YuDanyu WuYichun ChuKai Wang<h4>Objective</h4>To investigate the effects and mechanisms of miRNA 221 on myocardial ischemia/reperfusion injury (MIRI) in mice through the regulation of phospholamban (PLB) expression.<h4>Methods</h4>The MIRI mouse model was created and mice were divided into sham, MIRI, MIRI+ 221, and MIRI+ scr groups, with miRNA 221 overexpression induced in the myocardium of MIRI mice by targeted myocardial injection. Quantitative RT-PCR analysis was performed to observe the variation in miRNA 221, PLB, SERCA2, RYR2, NCX1, Cyt C and caspase 3 mRNA levels in myocardium, while Western blot assessed the levels of PLB, p-PLB (Ser16), p-PLB (Thr17), SERCA2, RYR2, NCX1, Cyt C and caspase 3 proteins. Changes in the structural integrity of the mouse heart were identified with HE and MASSON staining, while TUNEL staining was used to evaluate the TUNEL-positive cells of cardiomyocytes. Changes in myocardium calcium concentration were detected with reagent kits and the targeting interaction between miRNA 221 and PLB was evaluated using a luciferase reporter assay.<h4>Results</h4>In the myocardium of MIRI mice, miRNA 221 level was significantly reduced, while the levels of PLB, p-PLB (Ser16), p-PLB (Thr17), and apoptosis-related genes caspase 3, and Cyt C were increased markedly, as well as calcium levels in myocardium. Following the overexpression of miRNA 221 in myocardium, there was a marked alleviation of myocardial injury and cardiomyocyte apoptosis and necrosis, significant enhancement of left ventricular systolic function, and marked decrease in the levels of PLB, p-PLB (Ser16), p-PLB (Thr17), caspase 3 and Cyt C, as well as a significant decrease in total calcium levels in myocardium.<h4>Conclusions</h4>miRNA 221 can alleviate myocardial injury in mouse myocardial ischemia/reperfusion by suppressing the expression of PLB, thus reducing calcium overload in myocardium.https://doi.org/10.1371/journal.pone.0316887 |
| spellingShingle | Hongyu Li Jimiao Qiu Chang Liu Guobing Yu Danyu Wu Yichun Chu Kai Wang MicroRNA-221 protects myocardial contractility in myocardial ischemia/reperfusion injury through phospholamban. PLoS ONE |
| title | MicroRNA-221 protects myocardial contractility in myocardial ischemia/reperfusion injury through phospholamban. |
| title_full | MicroRNA-221 protects myocardial contractility in myocardial ischemia/reperfusion injury through phospholamban. |
| title_fullStr | MicroRNA-221 protects myocardial contractility in myocardial ischemia/reperfusion injury through phospholamban. |
| title_full_unstemmed | MicroRNA-221 protects myocardial contractility in myocardial ischemia/reperfusion injury through phospholamban. |
| title_short | MicroRNA-221 protects myocardial contractility in myocardial ischemia/reperfusion injury through phospholamban. |
| title_sort | microrna 221 protects myocardial contractility in myocardial ischemia reperfusion injury through phospholamban |
| url | https://doi.org/10.1371/journal.pone.0316887 |
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