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Coupling factor 6 downregulates platelet endothelial cell adhesion molecule-1 via c-Src activation and acts as a

Akiko Kumagai1, Tomohiro Osanai, Chisato Katoh

  • 1Department of Cardiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.

Atherosclerosis
|February 5, 2008
PubMed

Insights

Coupling factor 6 (CF6) and angiotensin II (AngII) suppress Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) expression and nitric oxide (NO) release. CF6 acts via c-Src, while AngII involves NADPH oxidase, impacting endothelial cell function.

Area of Science:

  • Endothelial cell biology
  • Molecular signaling
  • Cardiovascular research

Background:

  • Coupling factor 6 (CF6), an ATP synthase component, inhibits prostacyclin and nitric oxide (NO) production.
  • Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) mediates shear-induced NO release.
  • Understanding the interplay between CF6, PECAM-1, and NO is crucial for vascular health.

Purpose of the Study:

  • To investigate the relationship between CF6 and PECAM-1.
  • To examine CF6's effects on PECAM-1 expression and shear-mediated NO release.
  • To compare CF6's mechanisms with those of angiotensin II (AngII).

Main Methods:

  • Human umbilical vein endothelial cells (HUVEC) and aortic endothelial cells (HAEC) were treated with CF6 or AngII.
  • PECAM-1 expression, c-Src activation, and eNOS phosphorylation were assessed.
  • Inhibitors of c-Src (PP1), ATPase (Efrapeptin), and NADPH oxidase (Apocinin) were used.
  • Shear stress was applied to evaluate NO release.

Main Results:

  • CF6 and AngII suppressed PECAM-1 gene and protein expression in HUVEC and HAEC.
  • Both CF6 and AngII activated c-Src, which was essential for PECAM-1 suppression.
  • CF6-induced suppression involved ATPase inhibition and acidification, while AngII's involved NADPH oxidase.
  • Shear-induced NO release and eNOS phosphorylation were attenuated by CF6 and AngII pretreatment.

Conclusions:

  • CF6 downregulates PECAM-1 expression through c-Src activation.
  • CF6 attenuates shear-induced NO release, likely by inhibiting eNOS phosphorylation.
  • These findings elucidate novel mechanisms of endothelial dysfunction involving CF6 and PECAM-1.

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