Division of Cardiology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Department of Vascular Surgery, Karolinska University Hospital, Stockholm, Sweden.
Am J Physiol Heart Circ Physiol. 2024 Dec 1;327(6):H1431-H1441. doi: 10.1152/ajpheart.00443.2024. Epub 2024 Oct 11.
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. 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.
内皮功能障碍是血管炎症的早期后果，也是导致心肌梗死的冠状动脉粥样硬化性疾病的驱动因素。红细胞 (RBC) 介导心血管风险患者的内皮功能障碍，但它们在急性心肌梗死患者中的作用尚不清楚。本研究旨在探讨 ST 段抬高型心肌梗死 (STEMI) 患者的 RBC 是否会引起内皮功能障碍，以及全身炎症在此效应中的作用。将 STEMI 患者和年龄匹配的健康对照者的 RBC 与大鼠主动脉段共同孵育 18 小时，然后评估内皮依赖性舒张 (EDR) 和内皮非依赖性舒张 (EIDR)。还分析 RBC 和主动脉段的精氨酸酶和氧化应激。根据入院时 C 反应蛋白 (CRP) 水平将患者分为不同组。与 STEMI 和 CRP <2 mg/L 患者以及健康对照组的 RBC 相比，STEMI 和 CRP ≥2 mg/L 患者的 RBC 诱导 EDR 受损，但不诱导 EIDR 受损。与 STEMI 和 CRP <2 mg/L 患者以及健康对照组的 RBC 孵育后，主动脉精氨酸酶 1 的表达增加。抑制精氨酸酶可预防 RBC 诱导的内皮功能障碍。与 STEMI 和 CRP <2 mg/L 患者以及健康对照组的 RBC 相比，STEMI 和 CRP ≥2 mg/L 患者的 RBC 产生的活性氧增加。NADPH 氧化酶对血管的抑制和超氧化物歧化酶的增加改善了 EDR。轻度炎症的 STEMI 患者的 RBC 诱导内皮功能障碍的机制涉及精氨酸酶 1 以及 NADPH 氧化酶引起的 RBC 和血管超氧化物增加。STEMI 和全身性炎症患者的 RBC 体外诱导内皮功能障碍。RBC 诱导的内皮功能障碍是通过增加精氨酸酶 1 和向氧化应激的氧化还原平衡转变来介导的。精氨酸酶或自由基的抑制可减轻内皮功能障碍。该研究表明，红细胞作为全身炎症和 STEMI 的关键因素值得关注。
