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.