Adenylate cyclase type 9 antagonizes cAMP accumulation and regulates endothelial signalling involved in

Yohann Rautureau1, Marianne Berlatie1, Daniel Rivas1

  • 1Montreal Heart Institute, Université de Montréal, Montreal, Canada.

Insights

Adenylate cyclase type 9 (ADCY9) regulates endothelial cell function and permeability, impacting atherosclerosis development. Its inactivation improves endothelial function and reduces atherosclerotic lesion progression in mice.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Endothelial Cell Biology

Background:

  • The adenylate cyclase type 9 (ADCY9) gene is implicated in atherosclerotic outcomes.
  • Previous studies in mice showed Adcy9 inactivation improves endothelial function and inhibits atherogenesis.

Purpose of the Study:

  • To investigate the role of ADCY9 in regulating endothelial signaling pathways relevant to atherosclerosis.

Main Methods:

  • Examined ADCY9 expression in mouse arteries.
  • Investigated the effects of ADCY9 manipulation on cAMP levels and endothelial cell function in vitro.
  • Assessed vasodilation, endothelial permeability, and VASP phosphorylation in response to various stimuli in mouse models and human cells.

Main Results:

  • ADCY9 is expressed in the endothelium and its inactivation enhances cAMP accumulation and potentiates vasodilation.
  • Adcy9 inactivation reduces endothelial permeability and inhibits atherogenesis.
  • ADCY9 manipulation affects VASP phosphorylation and RAP1 activity, influencing endothelial barrier function.

Conclusions:

  • ADCY9 is expressed in endothelial cells and plays a critical role in regulating local cAMP levels.
  • ADCY9 influences endothelial functions, including permeability, which are relevant to the pathogenesis of atherosclerosis.
Abstract

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