Expression and function of vascular endothelial growth factor receptors (Flt-1 and Flk-1) in vascular adventitial fibroblasts

Vascular endothelial growth factor receptors (VEGFRs) are previously considered to exist exclusively in endothelial cells. However, little is known if the receptors are expressed in other non-endothelial cells. In this study, we measured activation of two VEGFRs, Flk-1 and Flt-1, and their biological functions in cultured adventitial fibroblasts and injured rat carotid injury arteries induced by balloon angioplasty. Our results indicated that Fit-1, but not Flk-1, existed in adventitial fibroblasts. Angiotensin 11 increased FIt-1 protein expression in a time- and concentration-dependent manner. Adventitial fibroblast migration stimulated by vascular endothelial growth factor (VEGF) and placental growth factor (PIGF) required Flt-1 expression. The FIt-1-induced adventitial fibroblast migration was blocked by anti-FIt-1 neutralizing antibody and soluble VEGFR1 protein (sFIt-1). However, Flt-1 activation did not enhance cell proliferation. In addition, FIt-1 expression was significantly increased in the neointima and adventitia in injured rat carotid arteries. We concluded that functional expression of FIt-1 in adventitial fibroblasts might be an important mediator in the pathogenesis of vascular remodeling after arterial injury. (c) 2007 Elsevier Inc. All rights reserved.