Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Arterioscler Thromb Vasc Biol. 2001 Dec;21(12):1928-33.

Mast cell chymase inhibits smooth muscle cell growth and collagen expression in vitro: transforming growth factor-beta1-dependent and -independent effects.

Author information

  • 1Wihuri Research Institute, Helsinki, Finland.

Abstract

In the vulnerable areas of fibrous caps of advanced atherosclerotic lesions, chymase-containing mast cells are present. In such areas, the numbers of smooth muscle cells (SMCs) and the content of collagen are reduced. In this in vitro study, we found that the addition of chymase, isolated and purified from rat serosal mast cells, to cultured rat aortic SMCs of the synthetic phenotype (s-SMCs) inhibited their proliferation by blocking the G(0)/G(1)-->S transition in the cell cycle. Rat chymase and recombinant human chymase inhibited the expression of collagen type I and type III mRNA in s-SMCs and in human coronary arterial SMCs. The growth-inhibitory effect of chymase was partially reversed by addition to the culture medium of an antibody capable of neutralizing the activity of transforming growth factor-beta1 (TGF-beta1). Immunocytochemistry showed that the s-SMCs expressed and synthesized extracellular matrix-associated TGF-beta1. On exposure to mast cell chymase, the extracellular matrix-associated latent TGF-beta1 was released and activated, as demonstrated by immunoblotting and by an ELISA with TGF-beta1 type II receptor for capture. When added to s-SMCs, such chymase-released TGF-beta1 was capable of inhibiting their growth. In contrast, the inhibitory effect of chymase on collagen synthesis by s-SMCs did not depend on TGF-beta1. Taken together, the findings support the hypothesis that chymase released from activated mast cells in atherosclerotic plaques contributes to cap remodeling.

PMID:
11742866
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk