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Hypoxic erythrocyte...
Hypoxic erythrocytes mediate cardioprotection through activation of soluble guanylate cyclase and release of cyclic GMP
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- Yang, Jiangning (author)
- Karolinska Inst, Dept Med, Unit Cardiol, Stockholm, Sweden.;Karolinska Inst, Dept Med, Unit Cardiol, S-17176 Stockholm, Sweden.
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- Sundqvist, Michaela L (author)
- Gymnastik- och idrottshögskolan,Institutionen för fysiologi, nutrition och biomekanik
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- Zheng, Xiaowei (author)
- Karolinska Institutet,Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
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- Jiao, Tong (author)
- Karolinska Inst, Dept Med, Unit Cardiol, Stockholm, Sweden.
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- Collado, Aida (author)
- Karolinska Inst, Dept Med, Unit Cardiol, Stockholm, Sweden.
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- Tratsiakovich, Yahor (author)
- Karolinska Inst, Dept Med, Unit Cardiol, Stockholm, Sweden.
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- Mahdi, Ali (author)
- Karolinska Inst, Dept Med, Unit Cardiol, Stockholm, Sweden.
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- Tengbom, John (author)
- Karolinska Inst, Dept Med, Unit Cardiol, Stockholm, Sweden.
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- Mergia, Evanthia (author)
- Ruhr Univ Bochum, Inst Pharmacol & Toxicol, Bochum, Germany.
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- Catrina, Sergiu-Bogdan (author)
- Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
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- Zhou, Zhichao (author)
- Karolinska Inst, Dept Med, Unit Cardiol, Stockholm, Sweden.
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- Carlström, Mattias (author)
- Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
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- Akaike, Takaaki (author)
- Tohoku Univ, Grad Sch Med, Dept Environm Med & Mol Toxicol, Sendai, Japan.
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- Cortese-Krott, Miriam M. (author)
- Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Heinrich Heine Univ, Med Fac, Div Cardiol Pneumol & Vasc Med, Myocardial Infarct Lab, Dusseldorf, Germany.
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- Weitzberg, Eddie (author)
- Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
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- Lundberg, Jon O. (author)
- Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
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- Pernow, John (author)
- Karolinska Institutet,Karolinska Inst, Dept Med, Unit Cardiol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden.;Karolinska Inst, Dept Med, Unit Cardiol, S-17176 Stockholm, Sweden.
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Karolinska Inst, Dept Med, Unit Cardiol, Stockholm, Sweden;Karolinska Inst, Dept Med, Unit Cardiol, S-17176 Stockholm, Sweden. Institutionen för fysiologi, nutrition och biomekanik (creator_code:org_t)
- American Society For Clinical Investigation, 2023
- 2023
- English.
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In: Journal of Clinical Investigation. - : American Society For Clinical Investigation. - 0021-9738 .- 1558-8238. ; 133:17
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https://gih.diva-por... (primary) (Raw object)
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Abstract
Subject headings
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- Red blood cells (RBCs) mediate cardioprotection via nitric oxide-like bioactivity, but the signaling and the identity of any mediator released by the RBCs remains unknown. We investigated whether RBCs exposed to hypoxia release a cardioprotective mediator and explored the nature of this mediator. Perfusion of isolated hearts subjected to ischemia-reperfusion with extracellular supernatant from mouse RBCs exposed to hypoxia resulted in improved postischemic cardiac function and reduced infarct size. Hypoxia increased extracellular export of cyclic guanosine monophosphate (cGMP) from mouse RBCs, and exogenous cGMP mimicked the cardioprotection induced by the supernatant. The protection induced by hypoxic RBCs was dependent on RBC-soluble guanylate cyclase and cGMP transport and was sensitive to phosphodiesterase 5 and activated cardiomyocyte protein kinase G. Oral administration of nitrate to mice to increase nitric oxide bioactivity further enhanced the cardioprotective effect of hypoxic RBCs. In a placebo-controlled clinical trial, a clear cardioprotective, soluble guanylate cyclase-dependent effect was induced by RBCs collected from patients randomized to 5 weeks nitrate-rich diet. It is concluded that RBCs generate and export cGMP as a response to hypoxia, mediating cardioprotection via a paracrine effect. This effect can be further augmented by a simple dietary intervention, suggesting preventive and therapeutic opportunities in ischemic heart disease.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Keyword
- Medicin/Teknik
- Medicine/Technology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Yang, Jiangning
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Sundqvist, Micha ...
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Zheng, Xiaowei
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Jiao, Tong
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Collado, Aida
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Tratsiakovich, Y ...
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show more...
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Mahdi, Ali
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Tengbom, John
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Mergia, Evanthia
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Catrina, Sergiu- ...
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Zhou, Zhichao
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Carlström, Matti ...
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Akaike, Takaaki
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Cortese-Krott, M ...
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Weitzberg, Eddie
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Lundberg, Jon O.
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Pernow, John
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
- Articles in the publication
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Journal of Clini ...
- By the university
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The Swedish School of Sport and Health Sciences
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Karolinska Institutet