Increased ICAM-1 and PECAM-1 transcription levels in the heart of Apo-E deficient mice in comparison to wild type (C57BL6)

Thromb Haemost. 2001 May;85(5):908-14.

Abstract

Adhesion molecules and chemoattractants are thought to play a critical role in the homing of leukocytes to sites of vascular lesions. Apo-E deficiency in mice creates an atherosclerotic model that mimics vascular lesions in man. Little is known on the effect of Apo-E deficiency on expression of adhesion molecules in the hearts of these animals. In this study, male C57BL6 and Apo-E deficient mice were fed a chow diet over periods of time (0 to 20 weeks). The transcription levels of major adhesion molecules (ICAM-1, PECAM-1), present in the heart, were followed by northern blots. Immunohistochemistry was used to localize these adhesion molecules in the heart. Results show a significant increase in gene transcription levels of ICAM-1 and PECAM-1 in Apo-E animals, but not wild type, at 16 and 20 weeks of chow diet. Such increase in levels of transcription was not observed in younger Apo-E and C57BL6 animals (0, 6 weeks of diet). ICAM-1 and PECAM-1 were strongly expressed in the endocardium and heart microvessels. In contrast, VCAM-1 was poorly stained, with only an occasional expression on the endocardium and arterioles. Enhanced gene expression levels of heart ICAM-1 and PECAM-1 observed in Apo-E deficient mice, but not in control animals, appears to induce the initial stages of an inflammatory reaction. Such observations, not previously reported, may induce heart vascular remodeling.

Publication types

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

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency*
  • Apolipoproteins E / genetics
  • Apolipoproteins E / pharmacology
  • Arteriosclerosis / etiology
  • Cholesterol / blood
  • Coronary Vessels / chemistry
  • Coronary Vessels / cytology
  • Diet, Fat-Restricted
  • Endothelium, Vascular / chemistry
  • Gene Expression Regulation / drug effects
  • Immunohistochemistry
  • Intercellular Adhesion Molecule-1 / genetics*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocardium / chemistry
  • Myocardium / metabolism*
  • Platelet Endothelial Cell Adhesion Molecule-1 / genetics*
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • RNA, Messenger / analysis*
  • RNA, Messenger / drug effects

Substances

  • Apolipoproteins E
  • Platelet Endothelial Cell Adhesion Molecule-1
  • RNA, Messenger
  • Intercellular Adhesion Molecule-1
  • Cholesterol