Altered Expression of Early Cardiac Marker Genes in Circulating Cells of Patients With Hypertrophic Cardiomyopathy

Cardiovasc Pathol. Nov-Dec 2007;16(6):329-35. doi: 10.1016/j.carpath.2007.04.004. Epub 2007 Jun 20.

Abstract

Background: Early cardiac marker genes, such as cardiac-specific homeobox (Csx/Nkx2.5), myocardin, homeodomain only protein, GATA4, and myocyte enhancer factor 2C, are thought to participate in cardiomyocyte differentiation and to contribute to heart hypertrophy in animal models. In this study, we investigated whether the expression of early cardiac genes is altered in the peripheral blood of patients with hypertrophic cardiomyopathy.

Methods: Peripheral blood mononuclear cells were isolated from 30 consecutive hypertrophic cardiomyopathy patients and 20 healthy controls, and gene expression was determined by quantitative real-time reverse transcription-polymerase chain reaction.

Results: Csx/Nkx2.5, myocardin, and GATA4 expressions were significantly higher in hypertrophic cardiomyopathy patients by 5.14+/-0.89 (P<.001), 1.65+/-0.21 (P<.05), and 2.04+/-0.41 (P<.04) times, respectively, while homeodomain only protein showed a fourfold decrease in expression (P<.02) compared to controls. In addition, expression of the differentiation-specific marker genes beta-myosin heavy chain and smooth muscle myosin heavy chain was significantly higher in hypertrophic cardiomyopathy patients by 3.72+/-0.82 (P<.02) and 2.57+/-0.72 (P<.05) times, respectively, compared to controls. Myocyte enhancer factor 2C expression was not different between patients and controls. Furthermore, increased expression of GATA4, myocardin, and beta-myosin heavy chain positively correlated with increased left ventricular mass.

Conclusions: In conclusion, we found altered expressions of early cardiac marker genes and differentiation-specific marker genes in peripheral blood mononuclear cells of hypertrophic cardiomyopathy patients compared to control individuals, possibly reflecting changes in response to disease.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Cardiomyopathy, Hypertrophic / blood
  • Cardiomyopathy, Hypertrophic / genetics*
  • Cardiomyopathy, Hypertrophic / pathology
  • Case-Control Studies
  • Female
  • GATA4 Transcription Factor / blood
  • GATA4 Transcription Factor / genetics
  • Gene Expression Regulation*
  • Heart Ventricles / pathology
  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins / blood
  • Homeodomain Proteins / genetics
  • Humans
  • Hypertrophy, Left Ventricular / blood
  • Hypertrophy, Left Ventricular / genetics
  • Hypertrophy, Left Ventricular / pathology
  • Leukocytes, Mononuclear / chemistry*
  • Leukocytes, Mononuclear / pathology
  • MADS Domain Proteins / blood
  • MADS Domain Proteins / genetics
  • MEF2 Transcription Factors
  • Male
  • Middle Aged
  • Myogenic Regulatory Factors / blood
  • Myogenic Regulatory Factors / genetics
  • Myosin Heavy Chains / blood
  • Myosin Heavy Chains / genetics
  • Nuclear Proteins / blood
  • Nuclear Proteins / genetics
  • RNA, Messenger / blood
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trans-Activators / blood
  • Trans-Activators / genetics
  • Transcription Factors / blood
  • Transcription Factors / genetics
  • Tumor Suppressor Proteins / blood
  • Tumor Suppressor Proteins / genetics

Substances

  • Biomarkers
  • GATA4 Transcription Factor
  • GATA4 protein, human
  • HOP protein, human
  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins
  • MADS Domain Proteins
  • MEF2 Transcription Factors
  • MEF2C protein, human
  • Myogenic Regulatory Factors
  • NKX2-5 protein, human
  • Nuclear Proteins
  • RNA, Messenger
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Proteins
  • myocardin
  • Myosin Heavy Chains