Physiological genomics of human arteries: quantitative relationship between gene expression and arterial stiffness

Circulation. 2003 Oct 14;108(15):1845-51. doi: 10.1161/01.CIR.0000091407.86925.7A. Epub 2003 Oct 6.

Abstract

Background: Previous genomic studies with human tissues have compared differential gene expression between 2 conditions (ie, normal versus diseased) to identify altered gene expression in a binary manner; however, a potentially more informative approach is to correlate the levels of gene expression with quantitative physiological parameters.

Methods and results: In this study, we have used this approach to examine genes whose expression correlates with arterial stiffness in human aortic specimens. Our data identify 2 distinct groups of genes, those associated with cell signaling and those associated with the mechanical regulation of vascular structure (cytoskeletal-cell membrane-extracellular matrix). Although previous studies have concentrated on the contribution of the latter group toward arterial stiffness, our data suggest that changes in expression of signaling molecules play an equally important role. Alterations in the profiles of signaling molecules could be involved in the regulation of cell cytoskeletal organization, cell-matrix interactions, or the contractile state of the cell.

Conclusions: Although the influence of smooth muscle contraction/relaxation on arterial stiffness could be controversial, our provocative data would suggest that further studies on this subject are indicated.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aorta / metabolism*
  • Aorta / ultrastructure
  • Arteriosclerosis / genetics*
  • Arteriosclerosis / pathology
  • Blood Pressure
  • Coronary Artery Disease / genetics
  • Coronary Artery Disease / pathology
  • Cytoskeletal Proteins / biosynthesis
  • Cytoskeletal Proteins / genetics
  • Extracellular Matrix Proteins / biosynthesis
  • Extracellular Matrix Proteins / genetics
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation*
  • Genomics
  • Humans
  • Male
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics
  • Middle Aged
  • Muscle, Smooth, Vascular / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Proteoglycans / biosynthesis
  • Proteoglycans / genetics
  • Signal Transduction / genetics
  • Transcription, Genetic
  • Vascular Resistance / genetics
  • Vasoconstriction / genetics

Substances

  • Cytoskeletal Proteins
  • Extracellular Matrix Proteins
  • Membrane Proteins
  • Proteoglycans