Reduced microvascular density in non-ischemic myocardium of patients with recent non-ST-segment-elevation myocardial infarction

Int J Cardiol. 2013 Aug 10;167(3):1027-37. doi: 10.1016/j.ijcard.2012.03.075. Epub 2012 Mar 28.

Abstract

Background: Myocardial microvascular dysfunction has been implicated in the pathogenesis of myocardial infarction (MI). We tested the hypothesis that patients with MI have lower microvasculature density in myocardium remote from the site of infarction than patients with similar extent of coronary artery disease (CAD) without MI and examined the relationship between myocardial capillary length density and plasma levels of angiogenesis-related biomarkers.

Methods: We analyzed biopsies from non-ischemic left ventricular (LV) myocardium and measured plasma levels of angiogenesis-related biomarkers in patients undergoing coronary artery bypass graft surgery, 57 without previous MI (no-MI) and 27 with recent non-ST-segment-elevation MI (NSTEMI). Comparison was made with biopsies from 31 aortic stenosis (AS) patients and 6 patients with "normal" LV without CAD.

Results: Myocardial microvascular density of NSTEMI patients was approximately half the density of no-MI patients, and similar to AS patients. Whereas the reduced microvascular density of AS patients was accounted for by their cardiomyocyte hypertrophy, this was not the case for NSTEMI patients, who had higher diffusion radius/cardiomyocyte width ratio than no-MI, "normal" LV, and AS patients. NSTEMI patients had lower plasma levels of carboxymethyl lysine and low molecular weight fluorophores, higher vascular endothelial growth factor (VEGF) receptor-1/VEGF-A ratio, and higher endostatin and hepatocyte growth factor levels than no-MI patients.

Conclusions: Recent MI was associated with reduced microvasculature density in myocardium remote from the site of infarction and alteration in plasma levels of angiogenesis-related biomarkers.

Keywords: Advanced glycation end-product; Angiogenesis; Arteriole; Capillary; Coronary microvasculature; Myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Coronary Circulation / physiology*
  • Endostatins / biosynthesis
  • Endostatins / blood
  • Female
  • Hepatocyte Growth Factor / biosynthesis
  • Hepatocyte Growth Factor / blood
  • Humans
  • Male
  • Microvessels / physiology*
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / pathology*
  • Myocardial Infarction / physiopathology
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor Receptor-1 / biosynthesis
  • Vascular Endothelial Growth Factor Receptor-1 / blood

Substances

  • Endostatins
  • Vascular Endothelial Growth Factor A
  • Hepatocyte Growth Factor
  • Vascular Endothelial Growth Factor Receptor-1