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Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
08:43

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation

Published on: May 31, 2016

Role of Rho/Rho-kinase and NO/cGMP signaling pathways in vascular function prior to atherosclerosis

Mayumi Mori-Kawabe1, Hiromi Tsushima, Seigo Fujimoto

  • 1Department of Cellular and Molecular Pharmacology, Nagoya City University Graduate School of Medical Sciences, Japan. mkawabe@med.nagoya-cu.ac.jp

Journal of Atherosclerosis and Thrombosis
|September 17, 2009
PubMed
Abstract

Insights

Early atherosclerosis in mice shows altered vascular signaling. Smooth muscle contraction depends more on Rho-kinase, while endothelium-dependent relaxation via nitric oxide (NO)/cyclic GMP (cGMP) is enhanced.

Area of Science:

  • Cardiovascular Research
  • Vascular Biology
  • Molecular Signaling

Background:

  • Atherosclerosis is a cardiovascular disease with poorly understood early vascular signal transduction.
  • Investigating early changes in Rho/Rho-kinase and NO/cGMP pathways is crucial for understanding vascular function.
  • Early-stage atherosclerosis research requires examining signaling mechanisms before significant pathology develops.

Purpose of the Study:

  • To investigate the roles of Rho/Rho-kinase and NO/cGMP signaling pathways in the aorta of mice at the pre-atherosclerotic stage.
  • To compare vascular function and signaling between apolipoprotein E-deficient (apoE-KO) and wild-type (WT) mice.
  • To elucidate alterations in smooth muscle contraction and endothelium-dependent relaxation prior to atherosclerosis.

Main Methods:

  • Measurement of aortic tension, RhoA protein expression, Rho-kinase activity, and cGMP levels.
  • Preparation of endothelium-intact and -denuded aortas from apoE-KO and WT mice at 2 months of age.
  • Pharmacological assessment using phenylephrine (PE) and a Rho-kinase inhibitor (Y-27632), and acetylcholine for relaxation studies.

Main Results:

  • Endothelium-denuded aortas from apoE-KO mice showed reduced maximal contraction to PE compared to WT.
  • Rho-kinase inhibition more effectively reduced contraction in apoE-KO aortas, despite similar RhoA protein and Rho-kinase activity.
  • Endothelium-dependent relaxation to acetylcholine was enhanced in apoE-KO mice due to increased endothelial NO release and higher basal cGMP levels.

Conclusions:

  • Aorta prior to atherosclerosis exhibits increased dependency of alpha(1)-adrenergic receptor-mediated contraction on Rho-kinase activity.
  • Enhanced endothelium-dependent relaxation suggests intensified NO/cGMP pathway signaling in the early stages.
  • These findings highlight distinct alterations in vascular signaling pathways preceding overt atherosclerotic development.

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