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 Flt-1, but not Flk-1, existed in adventitial fibroblasts. Angiotensin II increased Flt-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 Flt-1-induced adventitial fibroblast migration was blocked by anti-Flt-1 neutralizing antibody and soluble VEGFR1 protein (sFlt-1). However, Flt-1 activation did not enhance cell proliferation. In addition, Flt-1 expression was significantly increased in the neointima and adventitia in injured rat carotid arteries. We concluded that functional expression of Flt-1 in adventitial fibroblasts might be an important mediator in the pathogenesis of vascular remodeling after arterial injury.
Jin
Xin
X
Laboratory of Vascular Biology, Institute of Health Science Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Ge
Xiaoli
X
Zhu
Ding-liang
DL
Yan
Chen
C
Chu
Yu-Feng
YF
Chen
Wen-dong
WD
Liu
Jianjun
J
Gao
Ping-jin
PJ
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D001158:Arteries / Q000293:injuries / Q000473:pathology; D002339:Carotid Arteries / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003238:Connective Tissue / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism* / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D017539:Tunica Intima / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A; D000804:Angiotensin II; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2