Translational issues for mitoprotective agents as adjunct to reperfusion therapy in patients with ST-segment elevation myocardial infarction
Bøtker, Hans Erik (Aarhus University Hospital (Aarhus, Dinamarca))
Cabrera-Fuentes, H. A. (Kazan (Volga Region) Federal University)
Ruiz Meana, Marisol (Hospital Universitari Vall d'Hebron)
Heusch, Gerd (University of Essen)
Ovize, Michel (Université de Lyon)

Date:	2020
Abstract:	Pre-clinical studies have indicated that mitoprotective drugs may add cardioprotection beyond rapid revascularization, antiplatelet therapy and risk modification. We review the clinical efficacy of mitoprotective drugs that have progressed to clinical testing comprising cyclosporine A, KAI-9803, MTP131 and TRO 40303. Whereas cyclosporine may reduce infarct size in patients undergoing primary angioplasty as evaluated by release of myocardial ischaemic biomarkers and infarct size imaging, the other drugs were not capable of demonstrating this effect in the clinical setting. The absent effect leaves the role of the mitochondrial permeability transition pore for reperfusion injury in humans unanswered and indicates that targeting one single mechanism to provide mitoprotection may not be efficient. Moreover, the lack of effect may relate to favourable outcome with current optimal therapy, but conditions such as age, sex, diabetes, dyslipidaemia and concurrent medications may also alter mitochondrial function. However, as long as the molecular structure of the pore remains unknown and specific inhibitors of its opening are lacking, the mitochondrial permeability transition pore remains a target for alleviation of reperfusion injury. Nevertheless, taking conditions such as ageing, sex, comorbidities and co-medication into account may be of paramount importance during the design of pre-clinical and clinical studies testing mitoprotective drugs.
Grants:	Instituto de Salud Carlos III PI19-0119
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Cyclosporine A ; Ischaemia ; Mitochondria ; Myocardial infarction ; Reperfusion
Published in:	Journal of Cellular and Molecular Medicine, Vol. 24 (january 2020) , p. 2717-2729, ISSN 1582-4934

DOI: 10.1111/jcmm.14953
PMID: 31967733

13 p, 498.1 KB

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