Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Increased expression of plasminogen activator inhibitor-1 in cardiomyocytes contributes to cardiac fibrosis after myocardial infarction

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Takeshita, K.
  • Hayashi, M.
  • Iino, S.
  • Kondo, T.
  • Inden, Y.
  • Iwase, M.
  • Kojima, T.
  • Hirai, M.
  • Ito, M.
  • Loskutoff, David J.
  • Saito, H.
  • Murohara, T.
  • Yamamoto, K.

publication date

  • February 2004

journal

  • American Journal of Pathology  Journal

abstract

  • Plasminogen activator inhibitor-1 (PAI-1) plays a critical role in tissue fibrosis by inactivating matrix metalloproteinases, which might effect on the progression of left ventricular dysfunction. However, little has been known about the expression of PAI-1 during cardiac remodeling. We used a mouse model of myocardial infarction (MI) by coronary ligation, in which the progression of left ventricular remodeling was confirmed by echocardiography. Histological examination showed that interstitial and perivascular fibrosis progressed in the post-MI (PMI) heart at 4 weeks after the procedure. We observed the dramatic induction of cardiac PAI-1 mRNA and PAI-1 antigen in plasma in the PMI mice, as compared with the sham-operated (sham) mice. In situ hybridization analysis demonstrated that strong signals for PAI-1 mRNA were localized to cardiomyocytes in the border of infarct area and around fibrous lesions, and to perivascular mononuclear cells, which seemed to be mast cells, only in hearts of the PMI mice. Importantly, less development of cardiac fibrosis after MI was observed in mice deficient in PAI-1 as compared to wild-type mice. The mRNA expression of cytokines, transforming growth factor-beta, and tumor necrosis factor-alpha, was also increased in hearts of the PMI mice, but not in the sham mice. These observations suggest that cardiomyocytes and mast cells contribute to the increased PAI-1 expression, resulting in the development of interstitial and perivascular fibrosis in the PMI heart, and that the regional induction of cytokines may be involved in this process.

subject areas

  • Animals
  • Cytokines
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Fibrosis
  • Immunohistochemistry
  • In Situ Hybridization
  • Mast Cells
  • Mice
  • Myocardial Infarction
  • Myocardium
  • Myocytes, Cardiac
  • Plasminogen Activator Inhibitor 1
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Ventricular Remodeling
scroll to property group menus

Identity

PubMed Central ID

  • PMC1602257

International Standard Serial Number (ISSN)

  • 0002-9440

Digital Object Identifier (DOI)

  • 10.1016/s0002-9440(10)63135-5

PubMed ID

  • 14742251
scroll to property group menus

Additional Document Info

start page

  • 449

end page

  • 456

volume

  • 164

issue

  • 2

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support