Atherosclerotic plaque smooth muscle cells have a distinct phenotype

Arterioscler Thromb Vasc Biol. 2004 Jul;24(7):1283-9. doi: 10.1161/01.ATV.0000132401.12275.0c. Epub 2004 May 13.

Abstract

Objective: The present study addresses the question, "Are plaque smooth muscles cells (SMCs) genetically distinct from medial SMCs as reflected by the ability to maintain a distinctive expression phenotype in vitro?"

Methods and results: Multiple cell strains were developed from carotid endarcterectomy specimens, and quadruplicate array hybridizations were completed for each sample. A new normalization protocol was developed and used to analyze the data. Permutation analysis suggests that most of the significant differences in expression could not have occurred by chance. A broad pattern of significant expression differences, consisting of almost 5% of the genes probed, was detected. Quantitative polymerase chain reaction (QPCR) confirmation was found in 70% of a subset of genes selected for validation.

Conclusions: The SMC cultures were nearly indistinguishable by morphological features, population doubling time, and sensitivity to cell death induced by Fas cross-linking. Surprisingly, array expression analysis identified differences so extensive that we conclude that plaque and medial SMCs are distinctly different SMC cell types.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / drug effects
  • Arteriosclerosis / pathology*
  • Cell Division
  • Cells, Cultured / drug effects
  • Cells, Cultured / metabolism
  • Cells, Cultured / pathology
  • Enzyme Induction
  • Extracellular Matrix Proteins / biosynthesis
  • Extracellular Matrix Proteins / genetics
  • Fas Ligand Protein
  • Gene Expression Profiling*
  • Glutathione Transferase / biosynthesis
  • Glutathione Transferase / genetics
  • Humans
  • Membrane Glycoproteins / physiology
  • Muscle Proteins / biosynthesis*
  • Muscle Proteins / genetics
  • Muscle, Smooth, Vascular / pathology*
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology*
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Polymerase Chain Reaction
  • Tunica Media / cytology
  • fas Receptor / physiology

Substances

  • Extracellular Matrix Proteins
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • Muscle Proteins
  • fas Receptor
  • Glutathione Transferase