Compensatory growth of coronary arterioles in postinfarcted heart: regional differences in DNA synthesis and growth factor/receptor expression patterns

Am J Physiol Heart Circ Physiol. 2006 Oct;291(4):H1686-93. doi: 10.1152/ajpheart.00307.2006. Epub 2006 May 19.

Abstract

Previous studies have not addressed regional differences in adaptive arteriolar growth in the surviving left ventricular (LV) myocardium after infarction in appropriately aged animals, namely middle-aged or older. Accordingly, we examined the adaptive postinfarction growth of arterioles in two distinct regions, i.e., the LV free wall (LVFW) and septum, of middle-aged rats. We induced a myocardial infarction (MI) in 12-mo-old rats to analyze 1) protein expression in VEGF/Flt-1/Flk-1 and angiopoietin (Ang)-1/Ang-2/Tie-2 systems, 2) the arteriolar DNA synthesis, 3) the extent of the arteriolar bed, and 4) the alteration in minimal coronary vascular resistance. In both regions, arteriolar DNA synthesis was activated between days 4 and 7 after MI. Whereas in the LVFW the degree of DNA synthesis declined between days 11 and 14 post-MI, it continued to rise in the septum, and at day 14, the percentage of the arterioles undergoing DNA synthesis was comparable in the LVFW and the septum (9.7 +/- 1.6 and 7 +/- 2.1%, respectively). Arteriolar DNA synthesis was mainly associated with upregulation of Ang-2 and Tie-2 in both LV regions. Although 4 wk after MI the arteriolar beds in the LVFW and the septum expanded to the size of sham-operated rats, this growth did not compensate for the greater minimal coronary vascular resistance in the former. Thus our findings suggest that 1) the dynamics in adaptive arteriolar growth were similar between the two regions, despite a delay in the septum; and 2) the perfusion deficit in post-MI rats cannot be accounted for by inadequate adaptive growth of arterioles.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiopoietin-2 / genetics
  • Angiopoietin-2 / metabolism
  • Animals
  • Arterioles / cytology
  • Arterioles / growth & development
  • Arterioles / metabolism
  • Cell Proliferation
  • Coronary Vessels / cytology
  • Coronary Vessels / growth & development*
  • Coronary Vessels / metabolism
  • DNA / biosynthesis*
  • Gene Expression Regulation
  • Growth Substances / genetics
  • Growth Substances / metabolism*
  • Heart Septum / metabolism
  • Heart Septum / pathology
  • Heart Ventricles / metabolism
  • Heart Ventricles / pathology
  • Male
  • Myocardial Infarction / genetics
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology*
  • Neovascularization, Physiologic / genetics
  • Neovascularization, Physiologic / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, TIE-2 / genetics
  • Receptor, TIE-2 / metabolism
  • Receptors, Growth Factor / genetics
  • Receptors, Growth Factor / metabolism*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-1 / genetics
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Angiopoietin-2
  • Growth Substances
  • Receptors, Growth Factor
  • Vascular Endothelial Growth Factor A
  • DNA
  • Flt1 protein, rat
  • Receptor, TIE-2
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor Receptor-2