Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Am J Cardiol. 2010 Oct 15;106(8):1118-23. doi: 10.1016/j.amjcard.2010.06.028.
Fatty acid-binding proteins (FABPs) 4 and 5 play coordinated roles in rodent models of inflammation, insulin resistance, and atherosclerosis, but little is known of their role in human disease. The aim of this study was to examine the hypothesis that plasma adipocyte and macrophage FABP4 and FABP5 levels would provide additive value in the association with metabolic and inflammatory risk factors for cardiovascular disease as well as subclinical atherosclerosis. Using the Penn Diabetes Heart Study (PDHS; n = 806), cross-sectional analysis of FABP4 and FABP5 levels with metabolic and inflammatory parameters and with coronary artery calcium, a measure of subclinical coronary atherosclerosis, was performed. FABP4 and FABP5 levels had strong independent associations with the metabolic syndrome (for a 1-SD change in FABP levels, odds ratio [OR] 1.85, 95% confidence interval [CI] 1.43 to 2.23, and OR 1.66, 95% CI 1.41 to 1.95, respectively) but had differential associations with metabolic syndrome components. FABP4 and FABP5 were also independently associated with C-reactive protein and interleukin-6 levels. FABP4 (OR 1.26, 95% CI 1.05 to 1.52) but not FABP5 (OR 1.13, 95% CI 0.97 to 1.32) was associated with the presence of coronary artery calcium. An integrated score combining FABP4 and FABP5 quartile data had even stronger associations with the metabolic syndrome, C-reactive protein, interleukin-6, and coronary artery calcium compared to either FABP alone. In conclusion, this study provides evidence for an additive relation of FABP4 and FABP5 with the metabolic syndrome, inflammatory cardiovascular disease risk factors, and coronary atherosclerosis in type 2 diabetes mellitus. These findings suggest that FABP4 and FABP5 may represent mediators of and biomarkers for metabolic and cardiovascular disease in type 2 diabetes mellitus.
脂肪酸结合蛋白(FABP)4 和 5 在啮齿动物模型的炎症、胰岛素抵抗和动脉粥样硬化中发挥协调作用,但对其在人类疾病中的作用知之甚少。本研究旨在检验以下假设:血浆脂肪细胞和巨噬细胞 FABP4 和 FABP5 水平与心血管疾病代谢和炎症危险因素以及亚临床动脉粥样硬化的关联具有附加价值。利用宾夕法尼亚糖尿病心脏研究(PDHS;n=806),对 FABP4 和 FABP5 水平与代谢和炎症参数以及冠状动脉钙(亚临床冠状动脉粥样硬化的衡量标准)进行了横断面分析。FABP4 和 FABP5 水平与代谢综合征有很强的独立关联(FABP 水平的 1-SD 变化,比值比[OR]为 1.85,95%置信区间[CI]为 1.43 至 2.23,OR 为 1.66,95%CI 为 1.41 至 1.95),但与代谢综合征成分的关联存在差异。FABP4 和 FABP5 也与 C 反应蛋白和白细胞介素 6 水平独立相关。FABP4(OR 1.26,95%CI 1.05 至 1.52)但不是 FABP5(OR 1.13,95%CI 0.97 至 1.32)与冠状动脉钙的存在相关。将 FABP4 和 FABP5 四分位数数据结合起来的综合评分与代谢综合征、C 反应蛋白、白细胞介素 6 和冠状动脉钙的关联甚至比单独使用 FABP 更强。总之,本研究为 FABP4 和 FABP5 与 2 型糖尿病代谢综合征、炎症性心血管疾病危险因素和冠状动脉粥样硬化的附加关系提供了证据。这些发现表明,FABP4 和 FABP5 可能是 2 型糖尿病代谢和心血管疾病的介质和生物标志物。