Abstract 8890: Heart-Type Fatty Acid Binding Protein Impairs Angiogenesis via the Erk/stat1/vegf Signaling Pathway

Abstract

Introduction: Angiogenesis is an important process for repairing tissues after damage, including ischemic stroke, myocardial infraction, and ischemia. The heart-type fatty acid binding protein (H-FABP) is a cytoplasmic protein and previous studies indicated that the increased level of H-FABP was associated with acute coronary syndrome and ischemic stroke. Given the potential contribution of H-FABP to the pathological of cardiovascular diseases, it is important to know the direct mechanisms of H-FABP in angiogenesis. Methods and Results: Human coronary endothelial cells (HCAECs) and endothelial progenitor cells (EPCs) were used for the in vitro study. H-FABP treatments impaired the tubular formation, migration, and wound healing abilities of HCAECs and EPCs cultured from both stable coronary artery disease (CAD) patients and healthy subjects. H-FABP directly enhanced the phosphorylation of ERK and STAT-1. The inhibition of ERK by U0126 or the knockdown of STAT-1 by siRNA could reverse the damage of cell tubular formation and migration from H-FABP. Furthermore, exogenous of H-FABP could down-regulate the expression of VEGF. The administration of STAT-1 siRNA could reverse the level of VEGF reduced by H-FABP. In the matrigel plug neovascularization assay, the H-FABP-treated group had attenuated angiogenesis with decreased hemoglobin and capillary density levels. On the other hand, ox-LDL and TNF-α were used as stimulators in the in vitro experiments. The expressions of H-FABP were increased and the cell functions were impaired in the ox-LDL and TNF-α-treated cells. And, administration of H-FABP siRNA could recover the damage from ox-LDL and TNF-α. Conclusions: To sum up, we proved that H-FABP could directly impair angiogenesis via the ERK/STAT1/VEGF signaling pathway in endothelial cells, suggesting the critical role of H-FABP for vasculopathy. The findings of this study may not only improve our understanding about the critical mechanisms of vascular disease, but also provide the important rationale to the potential role of H-FABP as a novel therapeutic target in angiogenesis.