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Involvement of apoptosis signal-regulating kinase-1 on angiotensin II-induced monocyte chemoattractant protein-1

Takashi Omura1, Minoru Yoshiyama, Shokei Kim

  • 1Department of Internal Medicine and Cardiology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. omura@med.osaka-cu.ac.jp

Arteriosclerosis, Thrombosis, and Vascular Biology
|December 20, 2003
PubMed

Insights

Angiotensin II stimulates monocyte chemoattractant protein 1 (MCP-1) gene expression in cardiac fibroblasts, not cardiomyocytes. This process involves ASK-1, p38MAPK, and NF-kappaB signaling pathways, contributing to myocardial inflammation.

Area of Science:

  • Cardiovascular Biology
  • Molecular Mechanisms of Inflammation
  • Cell Signaling

Background:

  • Monocyte chemoattractant protein 1 (MCP-1) is implicated in leukocyte recruitment and chronic tissue damage.
  • The specific molecular pathways governing cardiac MCP-1 expression remain largely unelucidated.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying angiotensin II-induced MCP-1 expression in the heart.
  • To differentiate the response between cardiac fibroblasts and cardiomyocytes.

Main Methods:

  • Adenovirus gene transfer was employed to study MCP-1 expression in cultured rat neonatal ventricular cardiomyocytes and fibroblasts.
  • Stimulation with angiotensin II was used to assess gene expression and signaling pathway activation.
  • Involvement of ASK-1, p38MAPK, and NF-kappaB pathways was examined using wild-type and dominant-negative constructs.

Main Results:

  • Angiotensin II significantly upregulated MCP-1 mRNA in cardiac fibroblasts but not in cardiomyocytes.
  • Angiotensin II activated JNK, p38MAPK, and NF-kappaB signaling in cardiac fibroblasts.
  • ASK-1 activation promoted MCP-1 expression, while dominant-negative mutants of ASK-1 and p38MAPK, as well as pyrrolidine dithiocarbamate, inhibited it.

Conclusions:

  • Angiotensin II directly induces MCP-1 gene expression in cardiac fibroblasts.
  • The ASK-1-dependent activation of p38MAPK and NF-kappaB signaling pathways plays a partial role in angiotensin II-mediated myocardial MCP-1 expression.
Abstract

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