Journal article
DITPA stimulates arteriolar growth and modifies myocardial postinfarction remodeling
American journal of physiology. Heart and circulatory physiology, Vol.286(5), pp.H1994-2000
05/2004
DOI: 10.1152/ajpheart.00991.2003
PMID: 15072976
Abstract
Myocardial infarction (MI) is characterized by ventricular remodeling, hypertrophy of the surviving myocardium, and an insufficient angiogenic response. Thyroxine is a powerful stimulus for myocardial angiogenesis. Male rats that underwent coronary artery ligation and subsequent MI were given 3,5-diiodothyropropionic acid (DITPA; MI+DITPA group) during a 3-wk period. We evaluated ventricular remodeling using echocardiography and histology and myocardial vessel growth using image analysis. Protein expression was assessed using Western blotting and immunohistochemistry. This study tested the hypothesis that the thyroxine analog DITPA facilitates angiogenesis and influences postinfarction remodeling in the surviving hypertrophic myocardium. The increase in the region of akinesis (infarct expansion) was blunted in the MI+DITPA rats compared with the MI group (3 vs. 21%); the treated rats had smaller percent increases in the left ventricular (LV) volume (64 +/- 14 vs. 95 +/- 12) and the LV volume-to-mass ratio (47 +/- 13 vs. 84 +/- 10) as well as a blunted decrease in ejection fraction (-9 +/- 8 vs. -30 +/- 7%). Arteriolar length density was higher after treatment in the largest (>50% of the free wall) infarcts (64 +/- 3 vs. 43 +/- 7). Angiogenic growth factors [vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF)] and the angiopoietin receptor tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (Tie-2) values were elevated during the first week after infarction. DITPA did not cause additional increases in VEGF or Tie-2 values but did induce an increase in bFGF value after 3 days of treatment. This study provides the first evidence for an anatomical basis, i.e., attenuated ventricular remodeling and arteriolar growth, for improved function attributed to DITPA therapy of the infarcted heart. The favorable influences of DITPA on LV remodeling after large infarction are principally due to border zone preservation.
Details
- Title: Subtitle
- DITPA stimulates arteriolar growth and modifies myocardial postinfarction remodeling
- Creators
- Wei Zheng - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa 52242, USARobert M WeissXinguo WangRuifeng ZhouAngie M ArlenLi LeiEric LazartiguesRobert J Tomanek
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.286(5), pp.H1994-2000
- DOI
- 10.1152/ajpheart.00991.2003
- PMID
- 15072976
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Grant note
- HL-62587 / NHLBI NIH HHS
- Language
- English
- Date published
- 05/2004
- Academic Unit
- Anatomy and Cell Biology; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984094728202771
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