Increased Expression of Plasminogen Activator Inhibitor-1 in Cardiomyocytes Contributes to Cardiac Fibrosis after Myocardial Infarction
| Autor: | Takahisa Kondo, Koji Yamamoto, Toyoaki Murohara, Kyosuke Takeshita, Yasuya Inden, Tetsuhito Kojima, David J. Loskutoff, Masafumi Ito, Makoto Hirai, Shigeo Iino, Mutsuharu Hayashi, Hidehiko Saito, Mitsunori Iwase |
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| Rok vydání: | 2004 |
| Předmět: |
Pathology
medicine.medical_specialty Cardiac fibrosis Myocardial Infarction Enzyme-Linked Immunosorbent Assay Pathology and Forensic Medicine Mice chemistry.chemical_compound Transforming Growth Factor beta Plasminogen Activator Inhibitor 1 medicine Animals Myocyte Myocytes Cardiac Mast Cells RNA Messenger Myocardial infarction Ventricular remodeling In Situ Hybridization Ventricular Remodeling Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha business.industry Myocardium medicine.disease Fibrosis Immunohistochemistry Disease Models Animal chemistry Plasminogen activator inhibitor-1 Cytokines Tumor necrosis factor alpha Myocardial fibrosis business Plasminogen activator Regular Articles |
| Zdroj: | The American Journal of Pathology. 164:449-456 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/s0002-9440(10)63135-5 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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