The coronary endothelium: A target for vascular endothelial growth factor.Human coronary artery endothelial cells express functional receptors for vascular endothelial growth factor in vitro and in vivo

Vascular endothelial growth factor (VEGF) is an angiogenic peptide that can stimulate endothelial cell proliferation and migration in vitro and collat eral development in ischemic organs in vivo. Although postulated, the expre ssion of functional VEGF receptors in the heart has not been demonstrated y et. To prove this hypothesis and to extend the molecular basis of myocardia l angiogenesis, we have characterized the expression and function of VEGF r eceptors in human coronary artery endothelial cells (HCAEC) and in human he art tissue. VEGF strongly induces proliferation and migration of HCAEC. The se cells express transcripts of the two VEGF receptors KDR and Flt-1. Their expression levels are higher in HCAEC as compared with human umbilical vei n endothelial cells. In HCAEC, VEGF stimulates phosphorylation of KDR in a concentration-dependent manner proving that KDDR is a functional receptor t yrosine kinase. Scatchard analysis demonstrated the presence of the high af finity receptor Flt-1 in HCAEC with a kd of 8 pM. Flt-1 protein could be vi sualized as a single band corresponding to a size of 210 kd. In addition ma ture KDR protein could be detected in adult human heart. Taken together, HC AEC and human heart tissue express high levels of functional VEGF receptors . These results broaden the molecular basis for understanding and manipulat ing VEGF-induced endothelial function and angiogenesis in the coronary circ ulation.