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Piperine protects against pyroptosis in myocardial ischaemia/reperfusion injury by regulating the miR-383/RP105/AKT signalling pathway |
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| Authors: | Xin Guo Shan Hu Ji-Jun Liu Ling Huang Peng Zhong Zhi-Xing Fan Ping Ye Man-Hua Chen |
| Affiliation: | 1. Department of Cardiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;2. Heart Function Department, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Funding acquisition (equal), Investigation (equal), Methodology (equal), Project administration (equal);3. Department of Cardiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Contribution: Conceptualization (supporting), Data curation (supporting), Formal analysis (supporting);4. Department of Cardiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Contribution: Resources (equal), Software (equal), Supervision (equal), Validation (equal), Visualization (equal), Writing - original draft (equal);5. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China Contribution: Conceptualization (supporting), Data curation (supporting), Formal analysis (supporting), Funding acquisition (supporting), Methodology (equal);6. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China Contribution: Resources (supporting), Software (supporting), Supervision (supporting), Validation (supporting), Visualization (supporting);7. Department of Cardiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Contribution: Investigation (equal), Methodology (equal), Resources (supporting), Software (supporting), Supervision (supporting), Validation (supporting) |
| Abstract: | miRNA-mediated pyroptosis play crucial effects in the development of myocardial ischaemia/reperfusion (I/R) injury (MIRI). Piperine (PIP) possesses multiple pharmacological effects especially in I/R condition. This study focuses on whether PIP protects MIRI from pyroptosis via miR-383-dependent pathway. Rat MIRI model was established by 30 minutes of LAD ligation and 4 hours of reperfusion. Myocardial enzymes, histomorphology, structure and function were detected to evaluate MIRI. Recombinant adenoviral vectors for miR-383 overexpression or miR-383 silencing or RP105 knockdown were constructed, respectively. Luciferase reporter analysis was used to confirm RP105 as a target of miR-383. Pyroptosis-related markers were measured by Western blotting assay. The results showed that I/R provoked myocardial injury, as shown by the increases of LDH/CK releases, infarcted areas and apoptosis as well as worsened function and structure. Pyroptosis-related mediators including NLRP3, cleaved caspase-1, cleaved IL-1β and IL-18 were also reinforced after MIRI. However, PIP treatment greatly ameliorated MIRI in parallel with pyroptotic repression. In mechanistic studies, MIRI-caused elevation of miR-383 and decrease of RP105/PI3K/AKT pathway were reverted by PIP treatment. Luciferase reporter assay confirmed RP105 as a miR-383 target. miR-383 knockdown ameliorated but miR-383 overexpression facilitated pyroptosis and MIRI. Moreover, the anti-pyroptotic effect from miR-383 silencing was verified to be relied on the RP105/PI3K/AKT signalling pathway. Additionally, our present study further indicated the miR-383/RP105/AKT-dependent approach resulting from PIP administration against pyroptosis in MIRI. Therefore, PIP treatment attenuates MIRI and pyroptosis by regulating miR-383/RP105/AKT pathway, and it may provide a therapeutic manner for the treatment of MIRI. |
| Keywords: | ischaemia/reperfusion miR-383 PI3K/AKT piperine pyroptosis RP105 |