Phenotypic modulation of intima and media smooth muscle cells in fatal cases of coronary artery lesion

Arterioscler Thromb Vasc Biol. 2006 Feb;26(2):326-32. doi: 10.1161/01.ATV.0000199393.74656.4c. Epub 2005 Dec 8.

Abstract

Objective: Characterize the phenotypic features of media and intima coronary artery smooth muscle cells (SMCs) in mildly stenotic plaques, erosions, stable plaques, and in-stent restenosis.

Methods and results: Expression of alpha-smooth muscle actin (alpha-SMA), smooth muscle myosin heavy chains (SMMHCs), and smoothelin was investigated by immunohistochemistry followed by morphometric quantification. The cross-sectional area and the expression of cytoskeletal proteins in the media were lower in restenotic lesions and, to a lesser extent, in stable plaques compared with mildly stenotic plaques and erosions. An important expression of alpha-SMA was detected in the intima of the different lesions; moreover, alpha-SMA staining was significantly larger in erosions compared with all other conditions. In the same location, a striking decrease of SMMHCs and a disappearance of smoothelin were observed in all situations.

Conclusions: Medial atrophy is prevalent in restenotic lesions and stable plaques compared with mildly stenotic plaques and erosions. Intimal SMCs of all situations exhibit a phenotypic profile, suggesting that they have modulated into myofibroblasts (MFs). The high accumulation of alpha-SMA-positive MFs in erosions compared with stable plaques correlates with the higher appearance of thrombotic complications in this situation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Antigens, CD / metabolism
  • Antigens, CD34 / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Atrophy
  • Coronary Artery Disease / metabolism*
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / pathology*
  • Coronary Stenosis / metabolism
  • Coronary Stenosis / mortality
  • Coronary Stenosis / pathology
  • Coronary Vessels / metabolism*
  • Coronary Vessels / pathology*
  • Cytoskeletal Proteins / metabolism
  • Humans
  • Immunohistochemistry
  • Muscle Proteins / metabolism
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / pathology*
  • Myosin Heavy Chains / metabolism
  • Phenotype
  • Smooth Muscle Myosins / metabolism
  • Tunica Intima / metabolism
  • Tunica Intima / pathology
  • Tunica Media / metabolism
  • Tunica Media / pathology

Substances

  • Actins
  • Antigens, CD
  • Antigens, CD34
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Cytoskeletal Proteins
  • Muscle Proteins
  • SMTN protein, human
  • Smooth Muscle Myosins
  • Myosin Heavy Chains