Papotti Bianca, Opstad Trine Baur, Åkra Sissel, Tønnessen Theis, Braathen Bjørn, Hansen Charlotte Holst, Arnesen Harald, Solheim Svein, Seljeflot Ingebjørg, Ronda Nicoletta
Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital Ullevål, Oslo, Norway.
Department of Food and Drug, University of Parma, Parma, Italy.
Front Cardiovasc Med. 2023 Mar 2;10:1055069. doi: 10.3389/fcvm.2023.1055069. eCollection 2023.
Epicardial and pericardial adipose tissue (EAT and PAT) surround and protect the heart, with EAT directly sharing the microcirculation with the myocardium, possibly presenting a distinct macrophage phenotype that might affect the inflammatory environment in coronary heart disease (CHD). This study aims to investigate the expression of genes in different AT compartments driving the polarization of AT macrophages toward an anti-inflammatory (L-Galectin 9; CD206) or pro-inflammatory (NOS2) phenotype.
EAT, PAT, and subcutaneous (SAT) biopsies were collected from 52 CHD patients undergoing coronary artery bypass grafting, and from 22 CTRLs undergoing aortic valve replacement. L-Galectin9 (L-Gal9), CD206, and NOS2 AT gene expression and circulating levels were analyzed through RT-PCR and ELISA, respectively.
L-Gal9, CD206, and NOS2 gene expression was similar in all AT compartments in CHD and CTRLs, as were also L-Gal9 and CD206 circulating levels, while NOS2 serum levels were higher in CHD ( = 0.012 vs. CTRLs). In CTRLs, NOS2 expression was lower in EAT vs. SAT ( = 0.007), while in CHD patients CD206 expression was lower in both SAT and EAT as compared to PAT ( = 0.003, = 0.006, respectively), suggestive of a possible macrophage reprogramming toward a pro-inflammatory phenotype in EAT. In CHD patients, NOS2 expression in SAT correlated to that in PAT and EAT ( = 0.007, both), CD206 expression correlated positively to L-Gal9 ( < 0.001) only in EAT, and CD206 expression associated with that of macrophage identifying markers in all AT compartments ( < 0.001, all). In CHD patients, subjects with LDL-C above 1.8 mmol/L showed significantly higher NOS2 expression in PAT and EAT as compared to subjects with LDL-C levels below ( < 0.05), possibly reflecting increased cardiac AT pro-inflammatory activation. In SAT and PAT, CD206 expression associated with BMI in both CHD and CTRLs ( < 0.05, all), and with L-Gal9 in EAT, however only in CTRLs ( = 0.002).
CHD seems to be accompanied by an altered cardiac, and especially epicardial AT macrophage polarization. This may represent an important pathophysiological mechanism and a promising field of therapy targeting the excessive AT inflammation, in need of further investigation.
心外膜和心包脂肪组织（EAT和PAT）环绕并保护心脏，EAT直接与心肌共享微循环，可能呈现出独特的巨噬细胞表型，这可能会影响冠心病（CHD）中的炎症环境。本研究旨在调查不同脂肪组织区域中驱动脂肪组织巨噬细胞向抗炎（L-半乳糖凝集素9；CD206）或促炎（NOS2）表型极化的基因表达。
从52例接受冠状动脉搭桥术的冠心病患者以及22例接受主动脉瓣置换术的对照者中采集EAT、PAT和皮下（SAT）活检组织。分别通过逆转录聚合酶链反应（RT-PCR）和酶联免疫吸附测定（ELISA）分析L-半乳糖凝集素9（L-Gal9）、CD206和NOS2在脂肪组织中的基因表达及循环水平。
冠心病患者和对照者所有脂肪组织区域中L-Gal9、CD206和NOS2的基因表达相似，L-Gal9和CD206的循环水平也相似，而冠心病患者的NOS2血清水平更高（与对照者相比，P = 0.012）。在对照者中，EAT中NOS2的表达低于SAT（P = 0.007），而在冠心病患者中，与PAT相比，SAT和EAT中CD206的表达均较低（分别为P = 0.003和P = 0.006），提示EAT中巨噬细胞可能向促炎表型重编程。在冠心病患者中，SAT中NOS2的表达与PAT和EAT中的表达相关（均为P = 0.007），CD206的表达仅在EAT中与L-Gal9呈正相关（P < 0.001），并且CD206的表达与所有脂肪组织区域中巨噬细胞识别标志物的表达相关（均为P < 0.001）。在冠心病患者中，低密度脂蛋白胆固醇（LDL-C）高于1.8 mmol/L的受试者与LDL-C水平低于该值的受试者相比，PAT和EAT中NOS2的表达显著更高（P < 0.05），这可能反映了心脏脂肪组织促炎激活增加。在SAT和PAT中，CD206的表达在冠心病患者和对照者中均与体重指数（BMI）相关（均为P < 0.05），并且在EAT中与L-Gal9相关，但仅在对照者中如此（P = 0.002）。
冠心病似乎伴随着心脏尤其是心外膜脂肪组织巨噬细胞极化的改变。这可能代表一种重要的病理生理机制以及针对过度脂肪组织炎症的一个有前景的治疗领域，有待进一步研究。
