Capillary sprout endothelial cells exhibit a CD36 low phenotype: regulation by shear stress and vascular endothelial growth factor-induced mechanism for attenuating anti-proliferative thrombospondin-1 signaling

Am J Pathol. 2008 Oct;173(4):1220-8. doi: 10.2353/ajpath.2008.071194. Epub 2008 Sep 4.


Endothelial cells acquire distinctive molecular signatures in their transformation to an angiogenic phenotype that are indicative of changes in cell behavior and function. Using a rat mesentery model of inflammation-induced angiogenesis and a panel of known endothelial markers (CD31, VE-cadherin, BS-I lectin), we identified a capillary sprout-specific endothelial phenotype that is characterized by the marked down-regulation of CD36, a receptor for the anti-angiogenic molecule thrombospondin-1 (TSP-1). TSP-1/CD36 interactions were shown to regulate angiogenesis in this model as application of TSP-1 inhibited angiogenesis and blockade of both TSP-1 and CD36 accelerated angiogenesis. Vascular endothelial growth factor, which was up-regulated in the in vivo model, elicited a dose- and time-dependent down-regulation of CD36 (ie, to a CD36 low phenotype) in cultured human umbilical vein endothelial cells. Human umbilical vein endothelial cells that had been conditioned to a CD36 low phenotype with VEGF were found to be refractory to anti-proliferative TSP-1 signaling via a CD36-dependent mechanism. The loss of exposure to wall shear stress, which occurs in vivo when previously quiescent cells begin to sprout, also generated a CD36 low phenotype. Ultimately, our results identified the regulation of endothelial cell CD36 expression as a novel mechanism through which VEGF stimulates and sustains capillary sprouting in the presence of TSP-1. Additionally, CD36 was shown to function as a potential molecular linkage through which wall shear stress may regulate both microvessel sprouting and quiescence.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD36 Antigens / metabolism*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology*
  • Humans
  • Inflammation
  • Neovascularization, Pathologic / chemically induced
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Phenotype
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction* / drug effects
  • Stress, Mechanical
  • Thrombospondin 1 / metabolism*
  • Thrombospondin 1 / pharmacology
  • Time Factors
  • Up-Regulation / drug effects
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vascular Endothelial Growth Factor A / pharmacology


  • CD36 Antigens
  • Thrombospondin 1
  • Vascular Endothelial Growth Factor A