Simulated microgravity promotes nitric oxide-supported angiogenesis via the iNOS-cGMP-PKG pathway in macrovascular endothelial cells

FEBS Lett. 2010 Aug 4;584(15):3415-23. doi: 10.1016/j.febslet.2010.06.039. Epub 2010 Jul 1.

Abstract

Angiogenesis is a physiological process involving the growth of blood vessel in response to specific stimuli. The present study shows that limited microgravity treatments induce angiogenesis by activating macrovascular endothelial cells. Inhibition of nitric oxide production using pharmacological inhibitors and inducible nitric oxide synthase (iNOS) small interfering ribo nucleic acid (siRNA) abrogated microgravity induced nitric oxide production in macrovascular cells. The study further delineates that iNOS acts as a molecular switch for the heterogeneous effects of microgravity on macrovascular, endocardial and microvascular endothelial cells. Further dissection of nitric oxide downstream signaling confirms that simulated microgravity induces angiogenesis via the cyclic guanosine monophosphate (cGMP)-PKG dependent pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cell Movement
  • Cell Proliferation
  • Chickens
  • Cyclic GMP / metabolism*
  • Cyclic GMP-Dependent Protein Kinases / metabolism*
  • Endothelial Cells / cytology
  • Endothelial Cells / enzymology*
  • Humans
  • Neovascularization, Physiologic*
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type II / metabolism*
  • Nitric Oxide Synthase Type III / metabolism
  • Signal Transduction
  • Sus scrofa
  • Weightlessness
  • Weightlessness Simulation*
  • Wound Healing

Substances

  • Nitric Oxide
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Cyclic GMP-Dependent Protein Kinases
  • Cyclic GMP