Abstract 12913: Local Production of Fatty Acid-Binding Protein 4 Leads to Coronary Atherosclerosis
[Background] Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) is expressed in both adipocytes and macrophages, contributing to the development of insulin resistance and susceptibility to atherosclerosis. Recent studies have demonstrated secretion of FABP4 from adipocytes and a close relationship between increase of pericardial/perivascular adipose tissues and coronary atherosclerosis. We hypothesized that local production of FABP4 in pericardia/perivascular fat and macrophages in vascular plaques leads to the development of atherosclerosis. [Methods] We first examined whether there is arterio-venous gradient of FABP4 level in coronary circulation and whether the gradient, if any, associates with severity of coronary artery disease. In 34 male patients who underwent cardiac catheterization for suspected or known coronary artery diseases, blood samples for FABP4 assay were collected simultaneously from the aortic root (Ao) and coronary sinus (CS). Severity of coronary stenosis was assessed by use of a modified angiographic Gensini score. In the second series of study, we investigated the effect of exogenous FABP4 on inflammation and proliferation in human coronary artery smooth muscle cells (hCASMCs). [Results] Serum FABP4 level in CS (CS-FABP4) tended to be higher than that in Ao (Ao-FABP4). Levels of Ao-FABP4 and CS-FABP4 were positively correlated with age, body mass index (BMI), and plasma levels of glucose and insulin. Coronary stenosis score was weakly correlated with CS-FABP4 level, but not with Ao-FABP4 level. Stronger correlation (r = 0.59, p < 0.01) was observed for the relationship between coronary stenosis score and coronary veno-arterial difference in FABP4 level (CS-Ao-FABP4). Multivariate analyses adjusted by age, BMI, smoking, diabetes, dyslipidemia, and hypertension indicated that CS-Ao-FABP4 is an independent predictor of severity of coronary stenosis. In experiments in vitro, treatment of hCASMCs with recombinant FABP4 increased expression of proliferation and inflammation markers in a dose-dependent manner. [Conclusions] Present results support the notion that FABP4 locally produced by pericardial/perivascular fat and/or macrophages in vascular plaques contributes to development of coronary stenosis.
- © 2012 by American Heart Association, Inc.