Red blood cells from patients with ST-elevation myocardial infarction and elevated C-reactive protein levels induce endothelial dysfunction.

Autor:	Tengbom J; Division of Cardiology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Humoud R; Division of Cardiology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Kontidou E; Division of Cardiology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Jiao T; Division of Cardiology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Yang J; Division of Cardiology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Hedin U; Department of Vascular Surgery, Karolinska University Hospital, Stockholm, Sweden.; Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Zhou Z; Division of Cardiology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Jurga J; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden., Collado A; Division of Cardiology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Mahdi A; Division of Cardiology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden., Pernow J; Division of Cardiology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
Jazyk:	angličtina
Zdroj:	American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2024 Dec 01; Vol. 327 (6), pp. H1431-H1441. Date of Electronic Publication: 2024 Oct 11.
DOI:	10.1152/ajpheart.00443.2024
Abstrakt:	Endothelial dysfunction is an early consequence of vascular inflammation and a driver of coronary atherosclerotic disease leading to myocardial infarction. The red blood cells (RBCs) mediate endothelial dysfunction in patients at cardiovascular risk, but their role in patients with acute myocardial infarction is unknown. This study aimed to investigate if RBCs from patients with ST-elevation myocardial infarction (STEMI) induced endothelial dysfunction and the role of systemic inflammation in this effect. RBCs from patients with STEMI and aged-matched healthy controls were coincubated with rat aortic segments for 18 h followed by evaluation of endothelium-dependent (EDR) and endothelium-independent relaxation (EIDR). RBCs and aortic segments were also analyzed for arginase and oxidative stress. The patients were divided into groups depending on C-reactive protein (CRP) levels at admission. RBCs from patients with STEMI and CRP levels ≥2 mg/L induced impairment of EDR, but not EIDR, compared with RBCs from STEMI and CRP <2 mg/L and healthy controls. Aortic expression of arginase 1 was increased following incubation with RBCs from patients with STEMI and CRP ≥2, and arginase inhibition prevented the RBC-induced endothelial dysfunction. RBCs from patients with STEMI and CRP ≥2 had increased reactive oxygen species compared with RBCs from patients with CRP <2 and healthy controls. Vascular inhibition of NADPH oxidases and increased dismutation of superoxide improved EDR. RBCs from patients with STEMI and low-grade inflammation induce endothelial dysfunction through a mechanism involving arginase 1 as well as increased RBC and vascular superoxide by NADPH oxidases. NEW & NOTEWORTHY Red blood cells from patients with STEMI and systemic inflammation induce endothelial dysfunction ex vivo. The RBC-induced endothelial dysfunction is mediated through increased arginase 1 and a shift in the redox balance toward oxidative stress. Inhibition of arginase or free radicals attenuates the impairment of endothelial function. The study suggests that red blood cells deserve attention as a key player in systemic inflammation and STEMI.
Databáze:	MEDLINE
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