Cardiac remodeling by fibrous tissue after infarction in rats

Yao Sun, John Q. Zhang, Jiakun Zhang, Steffen Lamparter

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

After transmural myocardial infarction (MI), extensive myocardial remodeling by fibrous tissue appears in both infarcted and noninfarcted myocardium, which contributes to ventricular diastolic dysfunction. In the present study we sought to assess the time course of collagen remodeling in the infarcted rat hearts by detecting spatial and time-dependent cellular events related to collagen synthesis and degradation 2 to 28 days after left coronary artery ligation. In infarcted hearts, and compared with findings in sham-operated and unoperated rat hearts, we found the following: (1) macrophages infiltrated into sites of MI and visceral pericardium on day 2 and gradually disappeared after day 14; (2) myofibroblasts (MyoFb) first appeared at these sites of repair on day 3 and remained abundant thereafter at all time points examined; (3) transforming growth factor-β1 (TGF-β1) mRNA was enhanced in infarcted and noninfarcted myocardium on day 2 and remained throughout 28 days; (4) type I and III collagen mRNAs began to increase at and remote to MI on day 3 and remained elevated thereafter; (5) matrix metalloproteinase-1 mRNA was significantly increased at and remote to MI on day 3, declined to the control level on day 7, and remained low thereafter; (6) tissue inhibitor of matrix metalloproteinase (TIMP)-I, -II, and -III mRNAs were markedly elevated at sites of repair on day 3 and sustained throughout 28 days; (7) fibrillar collagen accumulation that was evident at and remote to MI on day 7 continued to accumulate thereafter at each site over 4 weeks. When compared with findings in unoperated rat heart, pericardial fibrosis was evident in both infarcted and noninfarcted heart, and the temporal response of collagen generation/degradation in pericardium was similar to that in infarcted myocardium. Thus collagen synthesis is activated in both infarcted and noninfarcted rat myocardium after transmural anterior infarction and is persistent throughout the 28-day period of study, whereas early collagen degradation is short lived and inactivated in the fibrogenic phase. Activated TGF-β1 mRNA expression is accompanied by the appearance of MyoFb and the expression of fibrillar collagens and TIMPs, suggesting that this fibrogenic cytokine may contribute to collagen remodeling in the rat heart after MI.

Original languageEnglish (US)
Pages (from-to)316-323
Number of pages8
JournalJournal of Laboratory and Clinical Medicine
Volume135
Issue number4
DOIs
StatePublished - Jan 1 2000

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Infarction
Rats
Collagen
Myocardial Infarction
Tissue
Myocardium
Messenger RNA
Fibrillar Collagens
Myofibroblasts
Pericardium
Transforming Growth Factors
Degradation
Repair
Ventricular Dysfunction
Tissue Inhibitor of Metalloproteinases
Matrix Metalloproteinase 1
Collagen Type III
Matrix Metalloproteinase Inhibitors
Collagen Type IV
Macrophages

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Cardiac remodeling by fibrous tissue after infarction in rats. / Sun, Yao; Zhang, John Q.; Zhang, Jiakun; Lamparter, Steffen.

In: Journal of Laboratory and Clinical Medicine, Vol. 135, No. 4, 01.01.2000, p. 316-323.

Research output: Contribution to journalArticle

Sun, Yao ; Zhang, John Q. ; Zhang, Jiakun ; Lamparter, Steffen. / Cardiac remodeling by fibrous tissue after infarction in rats. In: Journal of Laboratory and Clinical Medicine. 2000 ; Vol. 135, No. 4. pp. 316-323.
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