Post-ischemic myocardial fibrosis occurs independent of hemodynamic changes.

Abstract

OBJECTIVES:

Myocardial fibrosis is a major component of ventricular remodeling after large myocardial infarction (MI). The present study tests the hypothesis that post-ischemic myocardial fibrosis can occur independent of hemodynamic changes.

METHODS:

A mouse model of distal left coronary artery ligation was established to induce a small infarct (less than 15% of the left ventricle) in order to avoid significant mechanical overload after permanent myocardial ischemia. Left heart catheterization was performed to evaluate the post-infarct hemodynamics. Tissues from both ischemic and non-ischemic myocardium were examined for mRNA and protein expression at 24, 72 h and 7 days after ligation.

RESULTS:

Heart/body weight ratio after ligation was increased by approximately 10% over sham control although there is no statistically significant difference in hemodynamic parameters between the two groups. Non-ischemic myocardium distant from the infarct site showed molecular evidence of myocardial fibrosis 72 h and 7 days after ligation. There was marked up-regulation of mRNAs for extracellular matrix (ECM) proteins and their cross-linking enzyme, such as collagens type I, III and VI, and lysyl oxidase. Immunohistochemical study confirmed that the expression of these ECM proteins was significantly increased in the non-ischemic myocardium after 7 days. TGF-beta1 was up-regulated after 72 h in both ischemic and non-ischemic myocardium.

CONCLUSIONS:

Molecular and histopathological findings demonstrate that abnormal myocardial fibrosis can be induced by a small infarct independent of secondary hemodynamic changes.

• Authors: Takeshi Tsuda, Erhe Gao, Lucia Evangelisti, Dessislava Markova, Xinliang Ma, Mon-Li Chu
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 59 Issue 4 Pg. 926-33 (Oct 01 2003) ISSN: 0008-6363 [Print] England
• PMID: 14553832 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Extracellular Matrix Proteins
• Transforming Growth Factor beta
• Collagen

Topics

• Animals
• Collagen (analysis)
• Extracellular Matrix Proteins (analysis)
• Fibrosis
• Heart Rate
• Hemodynamics
• Immunohistochemistry (methods)
• Male
• Mice
• Mice, Inbred C57BL
• Myocardial Ischemia (pathology)
• Myocardium (pathology)
• Organ Size
• Reverse Transcriptase Polymerase Chain Reaction
• Stroke Volume
• Time Factors
• Transforming Growth Factor beta (analysis)
• Ventricular Remodeling