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Assessment of Vascular Regeneration in the CNS Using the Mouse Retina
07:32

Assessment of Vascular Regeneration in the CNS Using the Mouse Retina

Published on: June 23, 2014

Retinoid-induced expression and activity of an immediate early tumor suppressor gene in vascular smooth muscle cells

Jeffrey W Streb1, Xiaochun Long, Ting-Hein Lee

  • 1Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.

Plos One
|April 13, 2011
PubMed

Insights

Retinoids rapidly increase A-Kinase Anchoring Protein 12 beta (AKAP12β) expression, a tumor suppressor that inhibits vascular smooth muscle cell growth. This reveals a new mechanism for retinoid action in preventing vascular diseases.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Vascular Biology

Background:

  • Retinoids are clinically used for hyper-proliferative disorders.
  • Retinoids experimentally attenuate vascular occlusive diseases.
  • Retinoid action is mediated through retinoic acid response elements (RAREs).

Purpose of the Study:

  • To investigate the molecular mechanisms of retinoid action in vascular smooth muscle cells (SMC).
  • To identify novel retinoid-induced genes involved in vascular health.
  • To explore the role of AKAP12β in retinoid-mediated anti-proliferative effects.

Main Methods:

  • Studied retinoid induction of AKAP12β mRNA and protein in cultured SMC and intact vessel walls.
  • Performed expression kinetics and actinomycin D studies to determine gene regulation.
  • Analyzed Akap12β promoter for RAREs and used immunofluorescence microscopy and PKA overlay assays.
  • Assessed SMC growth in vitro and AKAP12 expression in experimentally-injured mouse vessels and human atheromatous lesions.

Main Results:

  • Retinoids rapidly induce AKAP12β mRNA and protein expression in SMC and vessel walls.
  • Akap12β is a retinoid-induced, immediate-early gene with a conserved RARE in its promoter.
  • AKAP12β physically associates with protein kinase A (PKA) and attenuates SMC growth.
  • AKAP12 expression is decreased in injured vessels and human atherosclerotic lesions.

Conclusions:

  • Retinoids induce the tumor suppressor AKAP12β, which inhibits vascular SMC proliferation.
  • This identifies a novel retinoid-induced pathway targeting vascular SMC growth.
  • Provides molecular insight into retinoid's anti-proliferative effects in the injured vessel wall.

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