2023-09-01 カロリンスカ研究所(KI)
◆研究者は今後、酸素不足の際に体の組織と細胞を保護するための赤血球の保護信号メカニズムを活性化する薬剤の開発と、保護信号の伝達メカニズムの調査を行う予定です。この研究結果は、心筋梗塞のリスクがある患者にとって重要な意義を持つ可能性があります。
◆この研究は、カロリンスカ研究所、カロリンスカ大学病院、東北大学、ハインリッヒ・ハイネ大学(ドイツ)、ルール大学ボーフム(ドイツ)などの研究者による共同研究である。
<関連情報>
- https://news.ki.se/red-blood-cells-exposed-to-oxygen-deficiency-protect-against-myocardial-infarction
- https://www.jci.org/articles/view/167693
低酸素状態の赤血球は、可溶性グアニル酸シクラーゼの活性化とサイクリックGMPの放出を通じて心筋保護を媒介する。 Hypoxic erythrocytes mediate cardioprotection through activation of soluble guanylate cyclase and release of cyclic GMP
Jiangning Yang,Michaela L. Sundqvist,Xiaowei Zheng,Tong Jiao,Aida Collado,Yahor Tratsiakovich,Ali Mahdi,John Tengbom,Evanthia Mergia,Sergiu-Bogdan Catrina,Zhichao Zhou,Mattias Carlström,Takaaki Akaike,Miriam M. Cortese-Krott,Eddie Weitzberg,Jon O. Lundberg,and John Pernow
Journal of Clinical Investigation Published September 1, 2023
DOI:https://doi.org/10.1172/JCI167693
Abstract
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.
