Translational issues for mitoprotective agents as adjunct to reperfusion therapy in patients with ST-segment elevation myocardial infarction

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperReviewResearchpeer-review

Standard

Translational issues for mitoprotective agents as adjunct to reperfusion therapy in patients with ST-segment elevation myocardial infarction. / Bøtker, Hans Erik; Cabrera-Fuentes, Hector Alejandro; Ruiz-Meana, Marisol; Heusch, Gerd; Ovize, Michel.

In: Journal of Cellular and Molecular Medicine (Online), Vol. 24, No. 5, 03.2020, p. 2717-2729.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperReviewResearchpeer-review

Harvard

Bøtker, HE, Cabrera-Fuentes, HA, Ruiz-Meana, M, Heusch, G & Ovize, M 2020, 'Translational issues for mitoprotective agents as adjunct to reperfusion therapy in patients with ST-segment elevation myocardial infarction', Journal of Cellular and Molecular Medicine (Online), vol. 24, no. 5, pp. 2717-2729. https://doi.org/10.1111/jcmm.14953

APA

Bøtker, H. E., Cabrera-Fuentes, H. A., Ruiz-Meana, M., Heusch, G., & Ovize, M. (2020). Translational issues for mitoprotective agents as adjunct to reperfusion therapy in patients with ST-segment elevation myocardial infarction. Journal of Cellular and Molecular Medicine (Online), 24(5), 2717-2729. https://doi.org/10.1111/jcmm.14953

CBE

Bøtker HE, Cabrera-Fuentes HA, Ruiz-Meana M, Heusch G, Ovize M. 2020. Translational issues for mitoprotective agents as adjunct to reperfusion therapy in patients with ST-segment elevation myocardial infarction. Journal of Cellular and Molecular Medicine (Online). 24(5):2717-2729. https://doi.org/10.1111/jcmm.14953

MLA

Vancouver

Bøtker HE, Cabrera-Fuentes HA, Ruiz-Meana M, Heusch G, Ovize M. Translational issues for mitoprotective agents as adjunct to reperfusion therapy in patients with ST-segment elevation myocardial infarction. Journal of Cellular and Molecular Medicine (Online). 2020 Mar;24(5):2717-2729. https://doi.org/10.1111/jcmm.14953

Author

Bøtker, Hans Erik ; Cabrera-Fuentes, Hector Alejandro ; Ruiz-Meana, Marisol ; Heusch, Gerd ; Ovize, Michel. / Translational issues for mitoprotective agents as adjunct to reperfusion therapy in patients with ST-segment elevation myocardial infarction. In: Journal of Cellular and Molecular Medicine (Online). 2020 ; Vol. 24, No. 5. pp. 2717-2729.

Bibtex

@article{6d6f7ba61209480b88b61f5efef260df,
title = "Translational issues for mitoprotective agents as adjunct to reperfusion therapy in patients with ST-segment elevation myocardial infarction",
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.",
keywords = "cyclosporine A, ischaemia, mitochondria, myocardial infarction, reperfusion, ISCHEMIA/REPERFUSION INJURY, OXIDATIVE STRESS, PROTEIN-KINASE-C, PROTECTION, MITOCHONDRIAL PERMEABILITY TRANSITION, CYCLOSPORINE-A, ATP SYNTHASE, CARDIAC ISCHEMIA, PORE, CARDIOPROTECTION",
author = "B{\o}tker, {Hans Erik} and Cabrera-Fuentes, {Hector Alejandro} and Marisol Ruiz-Meana and Gerd Heusch and Michel Ovize",
note = "{\textcopyright} 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.",
year = "2020",
month = mar,
doi = "10.1111/jcmm.14953",
language = "English",
volume = "24",
pages = "2717--2729",
journal = "Journal of Cellular and Molecular Medicine (Online)",
issn = "1582-4934",
publisher = "Wiley-Blackwell Publishing Ltd.",
number = "5",

}

RIS

TY - JOUR

T1 - Translational issues for mitoprotective agents as adjunct to reperfusion therapy in patients with ST-segment elevation myocardial infarction

AU - Bøtker, Hans Erik

AU - Cabrera-Fuentes, Hector Alejandro

AU - Ruiz-Meana, Marisol

AU - Heusch, Gerd

AU - Ovize, Michel

N1 - © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

PY - 2020/3

Y1 - 2020/3

N2 - 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.

AB - 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.

KW - cyclosporine A

KW - ischaemia

KW - mitochondria

KW - myocardial infarction

KW - reperfusion

KW - ISCHEMIA/REPERFUSION INJURY

KW - OXIDATIVE STRESS

KW - PROTEIN-KINASE-C

KW - PROTECTION

KW - MITOCHONDRIAL PERMEABILITY TRANSITION

KW - CYCLOSPORINE-A

KW - ATP SYNTHASE

KW - CARDIAC ISCHEMIA

KW - PORE

KW - CARDIOPROTECTION

U2 - 10.1111/jcmm.14953

DO - 10.1111/jcmm.14953

M3 - Review

C2 - 31967733

VL - 24

SP - 2717

EP - 2729

JO - Journal of Cellular and Molecular Medicine (Online)

JF - Journal of Cellular and Molecular Medicine (Online)

SN - 1582-4934

IS - 5

ER -