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01.12.2023 | Original Contribution

Reduction in mitochondrial ROS improves oxidative phosphorylation and provides resilience to coronary endothelium in non-reperfused myocardial infarction

verfasst von: Rayane Brinck Teixeira, Melissa Pfeiffer, Peng Zhang, Ehtesham Shafique, Bonnie Rayta, Catherine Karbasiafshar, Nagib Ahsan, Frank W. Sellke, M. Ruhul Abid

Erschienen in: Basic Research in Cardiology | Ausgabe 1/2023

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Abstract

Recent studies demonstrated that mitochondrial antioxidant MnSOD that reduces mitochondrial (mito) reactive oxygen species (ROS) helps maintain an optimal balance between sub-cellular ROS levels in coronary vascular endothelial cells (ECs). However, it is not known whether EC-specific mito-ROS modulation provides resilience to coronary ECs after a non-reperfused acute myocardial infarction (MI). This study examined whether a reduction in endothelium-specific mito-ROS improves the survival and proliferation of coronary ECs in vivo. We generated a novel conditional binary transgenic animal model that overexpresses (OE) mitochondrial antioxidant MnSOD in an EC-specific manner (MnSOD-OE). EC-specific MnSOD-OE was validated in heart sections and mouse heart ECs (MHECs). Mitosox and mito-roGFP assays demonstrated that MnSOD-OE resulted in a 50% reduction in mito-ROS in MHEC. Control and MnSOD-OE mice were subject to non-reperfusion MI surgery, echocardiography, and heart harvest. In post-MI hearts, MnSOD-OE promoted EC proliferation (by 2.4 ± 0.9 fold) and coronary angiogenesis (by 3.4 ± 0.9 fold), reduced myocardial infarct size (by 27%), and improved left ventricle ejection fraction (by 16%) and fractional shortening (by 20%). Interestingly, proteomic and Western blot analyses demonstrated upregulation in mitochondrial complex I and oxidative phosphorylation (OXPHOS) proteins in MnSOD-OE MHECs. These MHECs also showed increased mitochondrial oxygen consumption rate (OCR) and membrane potential. These findings suggest that mito-ROS reduction in EC improves coronary angiogenesis and cardiac function in non-reperfused MI, which are associated with increased activation of OXPHOS in EC-mitochondria. Activation of an energy-efficient mechanism in EC may be a novel mechanism to confer resilience to coronary EC during MI.

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Titel: Reduction in mitochondrial ROS improves oxidative phosphorylation and provides resilience to coronary endothelium in non-reperfused myocardial infarction
verfasst von: Rayane Brinck Teixeira
Melissa Pfeiffer
Peng Zhang
Ehtesham Shafique
Bonnie Rayta
Catherine Karbasiafshar
Nagib Ahsan
Frank W. Sellke
M. Ruhul Abid
Publikationsdatum: 01.12.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Basic Research in Cardiology / Ausgabe 1/2023
Print ISSN: 0300-8428
Elektronische ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-022-00976-x

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Möglicherweise hängt es von der Art der Diabetesmedikamente ab, wie hoch das Risiko der Betroffenen ist, dass sich sehkraftgefährdende Komplikationen verschlimmern.

TAVI versus Klappenchirurgie: Neue Vergleichsstudie sorgt für Erstaunen

21.05.2024 TAVI Nachrichten

Bei schwerer Aortenstenose und obstruktiver KHK empfehlen die Leitlinien derzeit eine chirurgische Kombi-Behandlung aus Klappenersatz plus Bypass-OP. Diese Empfehlung wird allerdings jetzt durch eine aktuelle Studie infrage gestellt – mit überraschender Deutlichkeit.

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Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Reduction in mitochondrial ROS improves oxidative phosphorylation and provides resilience to coronary endothelium in non-reperfused myocardial infarction

Abstract

Neu im Fachgebiet Kardiologie

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

GLP-1-Agonisten können Fortschreiten diabetischer Retinopathie begünstigen

TAVI versus Klappenchirurgie: Neue Vergleichsstudie sorgt für Erstaunen

Update Kardiologie

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

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Weitere Artikel der Ausgabe 1/2023

Anti-angiogenic effect of exo-LncRNA TUG1 in myocardial infarction and modulation by remote ischemic conditioning

Three-vessel coronary infusion of cardiosphere-derived cells for the treatment of heart failure with preserved ejection fraction in a pre-clinical pig model

Recent advances on the role of monoamine oxidases in cardiac pathophysiology

The role of glycolytic metabolic pathways in cardiovascular disease and potential therapeutic approaches

Mitophagy for cardioprotection

Oxygen-sensing pathways below autoregulatory threshold act to sustain myocardial oxygen delivery during reductions in perfusion pressure

Neu im Fachgebiet Kardiologie

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

GLP-1-Agonisten können Fortschreiten diabetischer Retinopathie begünstigen

TAVI versus Klappenchirurgie: Neue Vergleichsstudie sorgt für Erstaunen

Update Kardiologie