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

Autor: Teixeira RB; Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Brown University Warren Alpert Medical School, 1 Hoppin Street, Providence, RI, 02903, USA., Pfeiffer M; Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Brown University Warren Alpert Medical School, 1 Hoppin Street, Providence, RI, 02903, USA., Zhang P; Vascular Research Laboratory/Providence VA Medical Center and Department of Medicine, Alpert Medical School of Brown University, Providence, RI, USA., Shafique E; Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Brown University Warren Alpert Medical School, 1 Hoppin Street, Providence, RI, 02903, USA., Rayta B; Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Brown University Warren Alpert Medical School, 1 Hoppin Street, Providence, RI, 02903, USA., Karbasiafshar C; Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Brown University Warren Alpert Medical School, 1 Hoppin Street, Providence, RI, 02903, USA., Ahsan N; Division of Biology and Medicine, Alpert Medical School, Brown University, Providence, RI, 02903, USA.; Proteomics Core Facility, Center for Cancer Research and Development, Rhode Island Hospital, Providence, RI, 02903, USA.; Department of Chemistry and Biochemistry, Mass Spectrometry, Proteomics and Metabolomics Core Facility, Stephenson Life Sciences Research Center, University of Oklahoma, Norman, OK, USA., Sellke FW; Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Brown University Warren Alpert Medical School, 1 Hoppin Street, Providence, RI, 02903, USA., Abid MR; Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Brown University Warren Alpert Medical School, 1 Hoppin Street, Providence, RI, 02903, USA. ruhul_abid@brown.edu.
Jazyk: angličtina
Zdroj: Basic research in cardiology [Basic Res Cardiol] 2023 Jan 13; Vol. 118 (1), pp. 3. Date of Electronic Publication: 2023 Jan 13.
DOI: 10.1007/s00395-022-00976-x
Abstrakt: 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.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)
Databáze: MEDLINE
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