Red Blood Cells in Type 2 Diabetes Impair Cardiac Post-Ischemic Recovery Through an Arginase-Dependent Modulation of Nitric Oxide Synthase and Reactive Oxygen Species
| العنوان: | Red Blood Cells in Type 2 Diabetes Impair Cardiac Post-Ischemic Recovery Through an Arginase-Dependent Modulation of Nitric Oxide Synthase and Reactive Oxygen Species |
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| المؤلفون: | John Pernow, Oskar Kövamees, Jon O. Lundberg, Yahor Tratsiakovich, Attila Kiss, Ali Mahdi, Jiangning Yang, Xiaowei Zheng, Kerstin Brismar, Michael Alvarsson, Zhichao Zhou, Sergiu-Bogdan Catrina, Tong Jiao |
| المصدر: | JACC: Basic to Translational Science |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, WT, wild type, medicine.medical_specialty, ABH, 2 (S)-amino-6-boronohexanoic acid, LVEDP, left ventricular end-diastolic pressure, NAC, N-acetylcysteine, Type 2 diabetes, 030204 cardiovascular system & hematology, medicine.disease_cause, Nitric oxide, 03 medical and health sciences, chemistry.chemical_compound, PRECLINICAL RESEARCH, 0302 clinical medicine, L-NAME, NG-nitro-L-arginine methyl ester, ROS, reactive oxygen species, LVEDP - Left ventricular end-diastolic pressure, Internal medicine, medicine, NOS, nitric oxide synthase, chemistry.chemical_classification, reactive oxygen species, Reactive oxygen species, NO, nitric oxide, biology, nitric oxide synthase, arginase, eNOS, endothelial nitric oxide synthase, KH, Krebs-Henseleit, RBC, red blood cell, medicine.disease, nor-NOHA, Nω-hydroxy-nor-L-arginine, dP/dt, the first derivative of left ventricular pressure, Arginase, Nitric oxide synthase, Red blood cell, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, chemistry, iNOS, inducible isoform of nitric oxide synthase, biology.protein, type 2 diabetes, Cardiology and Cardiovascular Medicine, Oxidative stress, red blood cells, LVDP, left ventricular developed pressure |
| الوصف: | Visual Abstract Highlights • RBCs from mice and patients with type 2 diabetes have increased arginase activity and production of reactive oxygen species. • RBCs from mice and patients with type 2 diabetes aggravate myocardial ischemia-reperfusion injury. • Inhibition of arginase in RBCs from mice and patients with type 2 diabetes improves post-ischemic myocardial recovery via reduced oxidative stress. • Inhibition of nitric oxide synthase in RBC reduces oxidative stress and restores post-ischemic myocardial functional recovery. • These data demonstrate a novel disease mechanism by which RBC drive post-ischemic cardiac dysfunction in type 2 diabetes. Summary This study tested the hypothesis that red blood cell (RBC) arginase represents a potential therapeutic target in ischemia-reperfusion in type 2 diabetes. Post-ischemic cardiac recovery was impaired in hearts from db/db mice compared with wild-type hearts. RBCs from mice and patients with type 2 diabetes attenuated post-ischemic cardiac recovery of nondiabetic hearts. This impaired cardiac recovery was reversed by inhibition of RBCs arginase or nitric oxide synthase. The results suggest that RBCs from type 2 diabetics impair cardiac tolerance to ischemia-reperfusion via a pathway involving arginase activity and nitric oxide synthase-dependent oxidative stress. |
| تدمد: | 2452-302X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6824ed43223ac5018e0e9118ebdbea35Test https://pubmed.ncbi.nlm.nih.gov/30175269Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6824ed43223ac5018e0e9118ebdbea35 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2452302X |
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