Altered expression of early cardiac marker genes in circulating cells of patients with hypertrophic cardiomyopathy.
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.
Kontaraki
Joanna E
JE
Department of Cardiology, University Hospital of Heraklion, PO Box 1352, Stavrakia, Heraklion, Crete, Greece. kontarak@med.uoc.gr <kontarak@med.uoc.gr>
Parthenakis
Fragiskos I
FI
Patrianakos
Alexandros P
AP
Karalis
Ioannis K
IK
Vardas
Panos E
PE
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D050991:GATA4 Transcription Factor / Q000097:blood / Q000235:genetics; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000473:pathology; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000097:blood / Q000235:genetics; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000235:genetics / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000737:chemistry* / Q000473:pathology; D026161:MADS Domain Proteins / Q000097:blood / Q000235:genetics; D064326:MEF2 Transcription Factors; D008297:Male; D008875:Middle Aged; D018006:Myogenic Regulatory Factors / Q000097:blood / Q000235:genetics; D018995:Myosin Heavy Chains / Q000097:blood / Q000235:genetics; D009687:Nuclear Proteins / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000097:blood / Q000235:genetics; D014157:Transcription Factors / Q000097:blood / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000097:blood / Q000235:genetics; D000099251:Myocardin
D015415:Biomarkers; D050991:GATA4 Transcription Factor; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D018995:Myosin Heavy Chains; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000099251:Myocardin; C484170:GATA4 protein, human; C476884:HOPX protein, human; C578040:MEF2C protein, human; C095552:NKX2-5 protein, human