Mouse model of myocardial remodelling after ischemia: role of intercellular adhesion molecule-1

Cardiovasc Res. 2001 Feb 1;49(2):399-407. doi: 10.1016/s0008-6363(00)00261-3.

Abstract

Objective: We studied the effects of temporary myocardial ischemia and reperfusion on myocyte injury and ventricular remodelling in wildtype and intercellular adhesion molecule-1- (ICAM-1) deficient mice.

Methods: ICAM-1-/- and ICAM-1+/+ mice were subjected to 30 min of myocardial ischemia and subsequent reperfusion for 2 h, 1 week and 3 weeks, respectively. The evaluation of tissue damage and scar size was performed with histological sections stained with hematoxilin and eosin. Serum levels of troponin T, creatine kinase and lactate dehydrogenase isoenzyme 1 were evaluated as an index of cardiac cellular damage. Immunohistological analysis was employed to determine cell compositions in ischemic regions.

Results: After myocardial ischemia (30 min) and 2 h reperfusion, elevation in serum troponin T, creatine kinase and lactate dehydrogenase isoenzyme 1 were found in both groups, but significantly reduced in ICAM-1-/- mice compared with wildtype mice (P<0.05). Absence of a functional ICAM-1 gene in ICAM-1-/- mice resulted in a marked reduction of ischemia-reperfusion injury at the early stage. The damage score and size of the infarct area were lower in ICAM-1 -/- mice by 30 min of ischemia and 2 h of reperfusion (1.4+/-0.54 vs. 2.4+/-0.47, P<0.05). The percentage of MAC-1-positive cells in the ischemic region and the border zone was also significantly diminished in groups of ICAM-1-/- mice. Surprisingly, the scar size in ventricles in animals 1 or 3 weeks after ischemia was similar between ICAM-1-/- and ICAM-1+/+ mice, although the number of infiltrated MAC-1 positive cells in the scar in wildtype mice was higher.

Conclusion: Our results demonstrate that the absence of ICAM-1 expression results in less myocardial damage induced by ischemia-reperfusion at the early stage, but does not influence the size of myocardial infarction and scar formation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Creatine Kinase / blood
  • Immunohistochemistry
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / physiology*
  • Isoenzymes / blood
  • L-Lactate Dehydrogenase / blood
  • Leukocytes / immunology
  • Macrophage-1 Antigen / analysis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Confocal
  • Models, Animal
  • Myocardial Reperfusion Injury / immunology
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology*
  • Myocardium / immunology
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Statistics, Nonparametric
  • Troponin T / blood
  • Ventricular Remodeling*

Substances

  • Isoenzymes
  • Macrophage-1 Antigen
  • Troponin T
  • Intercellular Adhesion Molecule-1
  • L-Lactate Dehydrogenase
  • lactate dehydrogenase 1
  • Creatine Kinase