Agra Rosa María, Fernández-Trasancos Ángel, Sierra Juan, González-Juanatey José Ramón, Eiras Sonia
Department of Cardiology and Coronary Unit, Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain.
Inflammation. 2014 Oct;37(5):1504-12. doi: 10.1007/s10753-014-9876-3.
S100A9 (calgranulin B) has inflammatory and oxidative stress properties and was found to be associated with atherosclerosis and obesity. One of the proteins that can regulate S100A9 transcription is p53, which is involved in cell cycle, apoptosis and adipogenesis. Thus, it triggers adipocyte enlargement and finally obesity. Because epicardial adipose tissue (EAT) volume and thickness is related to coronary artery disease (CAD), we studied the gene expression of this pathway in patients with cardiovascular disease and its association with obesity. Adipocytes and stromal cells from EAT and subcutaneous adipose tissue (SAT) from 48 patients who underwent coronary artery bypass graft and/or valve replacement were obtained after collagenase digestion and differential centrifugation. The expression levels of the involved genes on adipogenesis and cell cycle like fatty acid-binding protein (FABP) 4, retinol-binding protein (RBP)4, p53 and S100A9 were determined by real-time polymerase chain reaction (PCR). Adipocyte diameter was measured by optical microscopy. We found that epicardial adipocytes expressed significantly lower levels of adipogenic genes (FABP4 and RBP4) and cell cycle-related genes (S100A9 and p53) than subcutaneous adipocytes. However, in obese patients, upregulation of adipogenic and cell cycle-related genes in subcutaneous and epicardial adipocytes, respectively, was observed. The enlargement of adipocyte size was related to FABP4, S100A9 and p53 expression levels in stromal cells. But only the p53 association was maintained in epicardial stromal cells from obese patients (p=0.003). The expression of p53, but not S100A9, in epicardial stromal cells is related to adipocyte enlargement in obese patients with cardiovascular disease. These findings suggest new mechanisms for understanding the relationship between epicardial fat thickness, obesity and cardiovascular disease.
S100A9（钙粒蛋白B）具有炎症和氧化应激特性，且被发现与动脉粥样硬化和肥胖有关。能够调节S100A9转录的蛋白之一是p53，它参与细胞周期、细胞凋亡和脂肪生成。因此，它会引发脂肪细胞增大并最终导致肥胖。由于心外膜脂肪组织（EAT）的体积和厚度与冠状动脉疾病（CAD）相关，我们研究了该通路在心血管疾病患者中的基因表达及其与肥胖的关联。通过胶原酶消化和差速离心，从48例行冠状动脉搭桥术和/或瓣膜置换术的患者的EAT及皮下脂肪组织（SAT）中获取脂肪细胞和基质细胞。通过实时聚合酶链反应（PCR）测定参与脂肪生成和细胞周期的相关基因如脂肪酸结合蛋白（FABP）4、视黄醇结合蛋白（RBP）4、p53和S100A9的表达水平。通过光学显微镜测量脂肪细胞直径。我们发现，心外膜脂肪细胞中脂肪生成基因（FABP4和RBP4）以及细胞周期相关基因（S100A9和p53）的表达水平明显低于皮下脂肪细胞。然而，在肥胖患者中，分别观察到皮下和心外膜脂肪细胞中脂肪生成和细胞周期相关基因的上调。脂肪细胞大小的增大与基质细胞中FABP4、S100A9和p53的表达水平有关。但仅在肥胖患者的心外膜基质细胞中维持了p53的相关性（p = 0.003）。在患有心血管疾病的肥胖患者中，心外膜基质细胞中p53而非S100A9的表达与脂肪细胞增大有关。这些发现为理解心外膜脂肪厚度、肥胖与心血管疾病之间的关系提供了新机制。
