Laudanski Krzysztof, Antar Mohamed, Gad Hossam, Diedrich Daniel A
Department of Anesthesiology and Perioperative Care, Mayo Clinic, Rochester, MN, United States.
Front Med (Lausanne). 2025 Aug 18;12:1561886. doi: 10.3389/fmed.2025.1561886. eCollection 2025.
Monocyte chemoattractant protein 1 (MCP-1) plays a critical role in the transmigration of peripheral monocytes, a central mechanism underlying chronic inflammation. In this study, we investigate postoperative serum kinetics of MCP-1 as a potential contributor to postoperative neurocognitive decline, arteriosclerosis, and the development of organ failures.
Seventy-one patients undergoing elective cardiac surgery were included in this study. Serum samples were collected preoperatively (t), and postoperatively at 24 h (t), 7 days (t), and 3 months (t). MCP-1 levels were quantified in conjunction with other inflammatory markers and alarmins. Whole blood samples underwent lipopolysaccharide (LPS) stimulation to evaluate MCP-1 production capacity, and peripheral monocyte transcriptomes were analyzed. Surrogate markers of end-organ dysfunction, including markers of neurodegeneration, neuroinjury, vasculitis, and atherosclerosis, were assessed. Acute kidney failure was defined per the RIFLE criteria, and occurrences of cerebrovascular accidents (CVA), pulmonary embolism (PE), deep venous thrombosis (DVT), and dispositions were documented.
Cardiac surgery resulted in an acute increase in serum MCP-1 at 24 h, 7 days, and 3 months as compared to the presurgical baseline. MCP-4 levels were unchanged, while Regulated on Activation Normal T Cell Expressed and Secreted cytokine (RANTES) was significantly depleted after surgery. Except for a prior history of cerebrovascular accidents, other preoperative clinical conditions, duration of anesthesia, surgery, cross-clamp, estimated fluid loss, and transfusions did not influence t MCP-1 serum level. Perioperative use of non-steroidal anti-inflammatory drugs and opioids affected acute serum MCP-1 levels. At 3 months, patients undergoing coronary artery bypass graft (CABG) surgery exhibited the most pronounced elevation in MCP-1 compared to other cardiac surgery. Serum IL-6 at 24 h positively correlated with MCP-1 levels measured at 24 h, 7 days, and 3 months. Additionally, markers of neurodegeneration ( protein and amyloid -1-40), some vascular inflammation (FGF-23 and FGF-21), and atherosclerosis (LOX-1) demonstrated correlational relationships with MCP-1. Finally, patients experiencing postoperative cerebrovascular accidents demonstrated depressed levels of MCP-1 at 24 h, 7 days, and 3 months as compared to patients recovering uneventfully.
Serum MCP-1 levels were elevated for up to 3 months following cardiac surgery, even in patients who experienced an uneventful recovery. MCP-4 was unchanged, while RANTES depressed post-surgery. A significant correlation between MCP-1 and serum surrogate markers of brain injury, vascular inflammation, and atherosclerosis highlights MCP-1 as a potential biomarker and a possible mediator of adverse outcomes after cardiac surgery.
单核细胞趋化蛋白1(MCP-1)在外周单核细胞的迁移中起关键作用,这是慢性炎症的核心机制。在本研究中,我们调查了术后血清MCP-1的动力学变化,其可能是术后神经认知功能下降、动脉硬化和器官功能衰竭发生的原因之一。
本研究纳入了71例行择期心脏手术的患者。术前(t)、术后24小时(t)、7天(t)和3个月(t)采集血清样本。对MCP-1水平以及其他炎症标志物和警戒素进行定量分析。对全血样本进行脂多糖(LPS)刺激以评估MCP-1的产生能力,并分析外周单核细胞转录组。评估终末器官功能障碍的替代标志物,包括神经退行性变、神经损伤、血管炎和动脉粥样硬化的标志物。根据RIFLE标准定义急性肾衰竭,并记录脑血管意外(CVA)、肺栓塞(PE)、深静脉血栓形成(DVT)的发生情况及患者转归。
与术前基线相比,心脏手术导致术后24小时、7天和3个月时血清MCP-1急性升高。MCP-4水平未变,而活化正常T细胞表达和分泌的调节细胞因子(RANTES)在术后显著减少。除了既往有脑血管意外病史外,其他术前临床情况、麻醉时间、手术时间、主动脉阻断时间、估计失液量和输血情况均不影响t时MCP-1血清水平。围手术期使用非甾体类抗炎药和阿片类药物会影响急性血清MCP-1水平。在3个月时,与其他心脏手术相比,接受冠状动脉旁路移植术(CABG)的患者MCP-1升高最为明显。术后24小时的血清白细胞介素-6与术后24小时、7天和3个月时测得的MCP-1水平呈正相关。此外,神经退行性变标志物(蛋白和淀粉样蛋白-1-40)、一些血管炎症标志物(成纤维细胞生长因子-23和成纤维细胞生长因子-21)以及动脉粥样硬化标志物(凝集素样氧化低密度脂蛋白受体1,LOX-1)与MCP-1存在相关性。最后,与恢复顺利的患者相比,发生术后脑血管意外的患者在术后24小时、7天和3个月时MCP-1水平较低。
即使是恢复顺利的患者,心脏手术后血清MCP-1水平也会升高长达3个月。MCP-4未变,而RANTES在术后降低。MCP-1与脑损伤、血管炎症和动脉粥样硬化的血清替代标志物之间存在显著相关性,这突出了MCP-1作为心脏手术后潜在生物标志物和不良结局可能介导因素的作用。