Smooth muscle cells of human intracranial aneurysms assume phenotypic features similar to those of the atherosclerotic plaque

Cardiovasc Pathol. 2013 Sep-Oct;22(5):339-44. doi: 10.1016/j.carpath.2013.01.083. Epub 2013 Mar 5.

Abstract

Objectives: Characterize the phenotypic features of smooth muscle cells (SMCs) in the wall of human saccular intracranial aneurysms (sIAs).

Methods and results: We investigated by means of immunohistochemistry the expression of the cytoskeletal differentiation markers α-smooth muscle actin (α-SMA), smooth muscle myosin heavy chains (SMMHCs), and smoothelin in 26 sIAs and 15 nonaneurysmal cerebral arteries. In addition, S100A4, a recently identified marker of dedifferentiated SMCs in atherosclerotic plaques, was also investigated. Six sIAs and 5 nonaneurysmal arteries were used for morphometric analysis. sIAs displayed a significant medial atrophy compared with nonaneurysmal cerebral arteries; moreover, sIA SMCs showed marked decrease of α-SMA and SMMHCs expression and disappearance of smoothelin. Unexpectedly, S100A4 was strongly up-regulated in media SMCs of sIAs.

Conclusions: In sIAs, media SMCs acquire a dedifferentiated phenotype and show de novo expression of S100A4, characteristic features of atherosclerotic plaque SMCs.

Keywords: Atherosclerosis; CD68; Smooth muscle myosin heavy chains; Smoothelin; α-smooth muscle actin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / metabolism
  • Case-Control Studies
  • Cell Dedifferentiation
  • Cell Differentiation
  • Cerebral Arteries / metabolism
  • Cerebral Arteries / pathology
  • Cytoskeletal Proteins / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Intracranial Aneurysm / metabolism*
  • Intracranial Aneurysm / pathology*
  • Male
  • Middle Aged
  • Muscle Proteins / metabolism
  • Myocytes, Smooth Muscle / metabolism*
  • Myocytes, Smooth Muscle / pathology*
  • Myosin Heavy Chains / metabolism
  • Phenotype
  • Plaque, Atherosclerotic / metabolism*
  • Plaque, Atherosclerotic / pathology*
  • S100 Calcium-Binding Protein A4
  • S100 Proteins / metabolism

Substances

  • ACTA2 protein, human
  • Actins
  • Biomarkers
  • Cytoskeletal Proteins
  • Muscle Proteins
  • S100 Calcium-Binding Protein A4
  • S100 Proteins
  • SMTN protein, human
  • S100A4 protein, human
  • Myosin Heavy Chains