Red blood cell eNOS is cardioprotective in acute myocardial infarction
Red blood cells (RBCs) were shown to transport and release nitric oxide (NO) bioactivity and carry an endothelial NO synthase (eNOS). However, the pathophysiological significance of RBC eNOS for cardioprotection in vivo is unknown. Here we aimed to analyze the role of RBC eNOS in the regulation of c...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-08-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231722001422 |
| _version_ | 1811322935407804416 |
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| author | Miriam M. Cortese-Krott Tatsiana Suvorava Francesca Leo Sophia K. Heuser Anthea LoBue Junjie Li Stefanie Becher Rebekka Schneckmann Tanu Srivrastava Ralf Erkens Georg Wolff Joachim P. Schmitt Maria Grandoch Jon O. Lundberg John Pernow Brant E. Isakson Eddie Weitzberg Malte Kelm |
| author_facet | Miriam M. Cortese-Krott Tatsiana Suvorava Francesca Leo Sophia K. Heuser Anthea LoBue Junjie Li Stefanie Becher Rebekka Schneckmann Tanu Srivrastava Ralf Erkens Georg Wolff Joachim P. Schmitt Maria Grandoch Jon O. Lundberg John Pernow Brant E. Isakson Eddie Weitzberg Malte Kelm |
| author_sort | Miriam M. Cortese-Krott |
| collection | DOAJ |
| description | Red blood cells (RBCs) were shown to transport and release nitric oxide (NO) bioactivity and carry an endothelial NO synthase (eNOS). However, the pathophysiological significance of RBC eNOS for cardioprotection in vivo is unknown. Here we aimed to analyze the role of RBC eNOS in the regulation of coronary blood flow, cardiac performance, and acute myocardial infarction (AMI) in vivo. To specifically distinguish the role of RBC eNOS from the endothelial cell (EC) eNOS, we generated RBC- and EC-specific knock-out (KO) and knock-in (KI) mice by Cre-induced inactivation or reactivation of eNOS. We found that RBC eNOS KO mice had fully preserved coronary dilatory responses and LV function. Instead, EC eNOS KO mice had a decreased coronary flow response in isolated perfused hearts and an increased LV developed pressure in response to elevated arterial pressure, while stroke volume was preserved. Interestingly, RBC eNOS KO showed a significantly increased infarct size and aggravated LV dysfunction with decreased stroke volume and cardiac output. This is consistent with reduced NO bioavailability and oxygen delivery capacity in RBC eNOS KOs. Crucially, RBC eNOS KI mice had decreased infarct size and preserved LV function after AMI. In contrast, EC eNOS KO and EC eNOS KI had no differences in infarct size or LV dysfunction after AMI, as compared to the controls. These data demonstrate that EC eNOS controls coronary vasodilator function, but does not directly affect infarct size, while RBC eNOS limits infarct size in AMI. Therefore, RBC eNOS signaling may represent a novel target for interventions in ischemia/reperfusion after myocardial infarction. |
| first_indexed | 2024-04-13T13:44:58Z |
| format | Article |
| id | doaj.art-b3929b71cddb4e96b40d04fba5670f37 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-13T13:44:58Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-b3929b71cddb4e96b40d04fba5670f372022-12-22T02:44:31ZengElsevierRedox Biology2213-23172022-08-0154102370Red blood cell eNOS is cardioprotective in acute myocardial infarctionMiriam M. Cortese-Krott0Tatsiana Suvorava1Francesca Leo2Sophia K. Heuser3Anthea LoBue4Junjie Li5Stefanie Becher6Rebekka Schneckmann7Tanu Srivrastava8Ralf Erkens9Georg Wolff10Joachim P. Schmitt11Maria Grandoch12Jon O. Lundberg13John Pernow14Brant E. Isakson15Eddie Weitzberg16Malte Kelm17Myocardial Infarction Research Laboratory, Department of Cardiology, Pulmonology, and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; Cardiovascular Research Laboratory, Department of Cardiology Pneumology and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden; Corresponding author. Myocardial Infarction Research Laboratory, Department of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich-Heine-University of Düsseldorf Postfach, 128, Universitaetsstrasse 1, 40225, Düsseldorf, Germany.Myocardial Infarction Research Laboratory, Department of Cardiology, Pulmonology, and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; Cardiovascular Research Laboratory, Department of Cardiology Pneumology and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, GermanyMyocardial Infarction Research Laboratory, Department of Cardiology, Pulmonology, and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, GermanyMyocardial Infarction Research Laboratory, Department of Cardiology, Pulmonology, and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, GermanyMyocardial Infarction Research Laboratory, Department of Cardiology, Pulmonology, and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, GermanyMyocardial Infarction Research Laboratory, Department of Cardiology, Pulmonology, and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, GermanyCardiovascular Research Laboratory, Department of Cardiology Pneumology and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, GermanyDepartment of Pharmacology and Clinical Pharmacology, Medical Faculty, Heinrich-Heine-University, GermanyDepartment of Pharmacology and Clinical Pharmacology, Medical Faculty, Heinrich-Heine-University, GermanyCardiovascular Research Laboratory, Department of Cardiology Pneumology and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, GermanyCardiovascular Research Laboratory, Department of Cardiology Pneumology and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, GermanyDepartment of Pharmacology and Clinical Pharmacology, Medical Faculty, Heinrich-Heine-University, GermanyDepartment of Pharmacology and Clinical Pharmacology, Medical Faculty, Heinrich-Heine-University, GermanyDepartment of Physiology and Pharmacology, Karolinska Institute, Stockholm, SwedenDepartment of Cardiology, Karolinska Institute, Stockholm, SwedenRobert M. Berne Cardiovascular Research Center, Department of Molecular Physiology and Biophysics, University of Virginia School of Medicine, Charlottesville, VA, USADepartment of Physiology and Pharmacology, Karolinska Institute, Stockholm, SwedenCardiovascular Research Laboratory, Department of Cardiology Pneumology and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany; CARID, Cardiovascular Research Institute Düsseldorf, Medical Faculty, Heinrich-Heine-University, Düsseldorf, GermanyRed blood cells (RBCs) were shown to transport and release nitric oxide (NO) bioactivity and carry an endothelial NO synthase (eNOS). However, the pathophysiological significance of RBC eNOS for cardioprotection in vivo is unknown. Here we aimed to analyze the role of RBC eNOS in the regulation of coronary blood flow, cardiac performance, and acute myocardial infarction (AMI) in vivo. To specifically distinguish the role of RBC eNOS from the endothelial cell (EC) eNOS, we generated RBC- and EC-specific knock-out (KO) and knock-in (KI) mice by Cre-induced inactivation or reactivation of eNOS. We found that RBC eNOS KO mice had fully preserved coronary dilatory responses and LV function. Instead, EC eNOS KO mice had a decreased coronary flow response in isolated perfused hearts and an increased LV developed pressure in response to elevated arterial pressure, while stroke volume was preserved. Interestingly, RBC eNOS KO showed a significantly increased infarct size and aggravated LV dysfunction with decreased stroke volume and cardiac output. This is consistent with reduced NO bioavailability and oxygen delivery capacity in RBC eNOS KOs. Crucially, RBC eNOS KI mice had decreased infarct size and preserved LV function after AMI. In contrast, EC eNOS KO and EC eNOS KI had no differences in infarct size or LV dysfunction after AMI, as compared to the controls. These data demonstrate that EC eNOS controls coronary vasodilator function, but does not directly affect infarct size, while RBC eNOS limits infarct size in AMI. Therefore, RBC eNOS signaling may represent a novel target for interventions in ischemia/reperfusion after myocardial infarction.http://www.sciencedirect.com/science/article/pii/S2213231722001422Acute myocardial infarctionNitric oxide synthaseRed blood cellsCre/LoxP systemIschemia/reperfusion injury |
| spellingShingle | Miriam M. Cortese-Krott Tatsiana Suvorava Francesca Leo Sophia K. Heuser Anthea LoBue Junjie Li Stefanie Becher Rebekka Schneckmann Tanu Srivrastava Ralf Erkens Georg Wolff Joachim P. Schmitt Maria Grandoch Jon O. Lundberg John Pernow Brant E. Isakson Eddie Weitzberg Malte Kelm Red blood cell eNOS is cardioprotective in acute myocardial infarction Redox Biology Acute myocardial infarction Nitric oxide synthase Red blood cells Cre/LoxP system Ischemia/reperfusion injury |
| title | Red blood cell eNOS is cardioprotective in acute myocardial infarction |
| title_full | Red blood cell eNOS is cardioprotective in acute myocardial infarction |
| title_fullStr | Red blood cell eNOS is cardioprotective in acute myocardial infarction |
| title_full_unstemmed | Red blood cell eNOS is cardioprotective in acute myocardial infarction |
| title_short | Red blood cell eNOS is cardioprotective in acute myocardial infarction |
| title_sort | red blood cell enos is cardioprotective in acute myocardial infarction |
| topic | Acute myocardial infarction Nitric oxide synthase Red blood cells Cre/LoxP system Ischemia/reperfusion injury |
| url | http://www.sciencedirect.com/science/article/pii/S2213231722001422 |
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