Oxidative Stress and Vascular Smooth Muscle Cell Growth: A Mechanistic Linkage by Cyclophilin A

Kimio Satoh, Patrizia Nigro, Bradford C. Berk

Research output: Contribution to journalReview articlepeer-review

111 Citations (Scopus)

Abstract

Inflammation and oxidative stress contribute to the pathology of many diseases, but specific therapeutic targets remain elusive. Oxidative stress, generated by excessive reactive oxygen species (ROS), promotes cardiovascular disease. However, the precise mechanism of how ROS deteriorate vascular function and promote vascular remodeling in vivo has not been clearly elucidated. Cyclophilin A (CyPA) is a 20kD chaperone protein that is secreted from vascular smooth muscle cells (VSMC) in response to ROS, and stimulates VSMC proliferation and inflammatory cell migration in vitro and in vivo. CyPA (both intracellular and extracellular) contributes to inflammation and atherosclerosis by promoting endothelial cell (EC) apoptosis and EC expression of leukocyte adhesion molecules, stimulating leukocyte migration, enhancing T helper cell type 1 (Th1) responses, increasing proliferation of macrophages and vascular smooth muscle cells (VSMC), and increasing pro-inflammatory signal transduction in VSMC. We tested the hypothesis that CyPA contributes to cardiovascular diseases by analyzing several genetic interventions that include the CyPA knockout mouse and the CyPA overexpressing transgenic mouse (VSMC-Tg). CyPA plays a crucial role in VSMC proliferation/migration and inflammatory cell recruitment, resulting in cardiovascular diseases in vivo. Antioxid.

Original languageEnglish
Pages (from-to)675-682
Number of pages8
JournalAntioxidants and Redox Signaling
Volume12
Issue number5
DOIs
Publication statusPublished - 2010 Mar 1

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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