CD36 is Downregulated by VEGF‐A and the Removal of Wall Shear Stress: Implications for the Regulation of a CD36‐ Capillary Sprout Specific Endothelial Phenotype.

Abstract

Using a rat mesentery model of inflammation-induced angiogenesis, we recently identified a capillary sprout specific endothelial cell (EC) phenotype that is marked by the downregulation of CD36, a receptor for the anti-angiogenic molecule thrombospondin-1 (TSP-1). Consistent with a role for TSP-1/CD36 signaling in this model, applying TSP-1 (5 ug/ml) elicited a 35% decrease in vascularized area and a 30% decrease in length density. Neutralizing antibodies to TSP-1 or CD36 (20 ug/ml) elicited 25% increases in vascularized area. VEGF-A expression increases markedly in this model (2.5-fold by ELISA), so we tested whether VEGF-A could directly regulate the CD36- phenotype. Consistent with this hypothesis, VEGF-A (5–50 ng/ml) dose-dependently downregulated CD36 in HUVECS (41% of control at 50 ng/ml). In addition, because sprouting ECs lose contact with flow, we tested how the removal of wall shear stress (2 dyn/cm2) from HUVECS affected CD36 and found that CD36 was significantly downregulated. These results suggest that both VEGF-A and wall shear stress can control capillary stability and sprouting in the presence of TSP-1 through adjustments in EC CD36 expression. Supported by NIH HL74082 and NIH HL65958.