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. 2019 Dec;80(8):1013-1030.
doi: 10.1002/ddr.21593. Epub 2019 Aug 24.

Pharmacology of mitochondrial permeability transition pore inhibitors

Natalia V Naryzhnaya  1 , Leonid N Maslov  1 , Peter R Oeltgen  2
Affiliations

Pharmacology of mitochondrial permeability transition pore inhibitors

Natalia V Naryzhnaya et al. Drug Dev Res. 2019 Dec.

Abstract

It is now firmly established that an important event in the formation of reperfusion injury of the heart is the opening of mitochondrial permeability transition pores (mPTPs), which changes the permeability of the mitochondria. mPTP opening results in the death of cardiomyocytes through activation of apoptosis and necroptosis. Experimental studies have shown that pharmacological inhibition of mPTP opening promotes the reduction in the infarct size and the suppression of apoptosis. Indeed, studies have shown the efficacy of mPTP inhibitors in animal models of myocardial reperfusion and isolated human myocardial trabeculae. However, clinical trials of cyclosporin A and TRO40303 have not provided a clear answer to the question of the effectiveness of mPTP inhibitors in patients with acute myocardial infarction. This article presents an analysis of possible approaches for the pharmacological regulation of mPTP during reperfusion injury of the heart.

Keywords: heart; mitochondrial permeability transition pore; reperfusion.

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References

REFERENCES

    1. Adams, J. W., Pagel, A. L., Means, C. K., Oksenberg, D., Armstrong, R. C., & Brown, J. H. (2000). Cardiomyocyte apoptosis induced by Gαq Signaling is mediated by permeability transition pore formation and activation of the mitochondrial death pathway. Circulation Research, 87(12), 1180-1187. https://doi.org/10.1161/01.RES.87.12.1180
    1. Alavian, K. N., Beutner, G., Lazrove, E., Sacchetti, S., Park, H.-A., Licznerski, P., … Jonas, E. A. (2014). An uncoupling channel within the c-subunit ring of the F1FO ATP synthase is the mitochondrial permeability transition pore. Proceedings of the National Academy of Sciences, 111(29), 10580-10585. https://doi.org/10.1073/pnas.1401591111
    1. Anwar, M., Kasper, A., Steck, A. R., & Schier, J. G. (2017). Bongkrekic acid-A review of a lesser-known mitochondrial toxin. Journal of Medical Toxicology, 13(2), 173-179. https://doi.org/10.1007/s13181-016-0577-1
    1. Argaud, L., Gateauroesch, O., Muntean, D., Chalabreysse, L., Loufouat, J., Robert, D., & Ovize, M. (2005). Specific inhibition of the mitochondrial permeability transition prevents lethal reperfusion injury. Journal of Molecular and Cellular Cardiology, 38(2), 367-374. https://doi.org/10.1016/j.yjmcc.2004.12.001
    1. Atar, D., Arheden, H., Berdeaux, A., Bonnet, J.-L., Carlsson, M., Clemmensen, P., … Jensen, S. E. (2015). Effect of intravenous TRO40303 as an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: MITOCARE study results. European Heart Journal, 36(2), 112-119. https://doi.org/10.1093/eurheartj/ehu331

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