Ismail, Nur Izzah;
Michel, Nathaly Anto;
Katwadi, Khairunnisa;
Lim, Mim-Mim;
Chan, To-Kiu;
Rahman, Attaur;
Xu, Dachun;
... Ong, Sang-Bing; + view all
(2022)
Ischemic Preconditioning and Postconditioning Protect the Heart by Preserving the Mitochondrial Network.
BioMed Research International
, 2022
, Article 6889278. 10.1155/2022/6889278.
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Abstract
BACKGROUND: Mitochondria fuse to form elongated networks which are more tolerable to stress and injury. Ischemic pre- and postconditioning (IPC and IPost, respectively) are established cardioprotective strategies in the preclinical setting. Whether IPC and IPost modulates mitochondrial morphology is unknown. We hypothesize that the protective effects of IPC and IPost may be conferred via preservation of mitochondrial network. METHODS: IPC and IPost were applied to the H9c2 rat myoblast cells, isolated adult primary murine cardiomyocytes, and the Langendorff-isolated perfused rat hearts. The effects of IPC and IPost on cardiac cell death following ischemia-reperfusion injury (IRI), mitochondrial morphology, and gene expression of mitochondrial-shaping proteins were investigated. RESULTS: IPC and IPost successfully reduced cardiac cell death and myocardial infarct size. IPC and IPost maintained the mitochondrial network in both H9c2 and isolated adult primary murine cardiomyocytes. 2D-length measurement of the 3 mitochondrial subpopulations showed that IPC and IPost significantly increased the length of interfibrillar mitochondria (IFM). Gene expression of the pro-fusion protein, Mfn1, was significantly increased by IPC, while the pro-fission protein, Drp1, was significantly reduced by IPost in the H9c2 cells. In the primary cardiomyocytes, gene expression of both Mfn1 and Mfn2 were significantly upregulated by IPC and IPost, while Drp1 was significantly downregulated by IPost. In the Langendorff-isolated perfused heart, gene expression of Drp1 was significantly downregulated by both IPC and IPost. CONCLUSION: IPC and IPost-mediated upregulation of pro-fusion proteins (Mfn1 and Mfn2) and downregulation of pro-fission (Drp1) promote maintenance of the interconnected mitochondrial network, ultimately conferring cardioprotection against IRI.
| Type: | Article |
|---|---|
| Title: | Ischemic Preconditioning and Postconditioning Protect the Heart by Preserving the Mitochondrial Network |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1155/2022/6889278 |
| Publisher version: | https://doi.org/10.1155/2022%2F6889278 |
| Language: | English |
| Additional information: | © 2022 Nur Izzah Ismail et al. This is an open access article distributed under the Creative Commons Attribution Licens (https://creativecommons.org/licenses/by/4.0/). |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10156678 |
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