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.
Subject(s)
Cardiomyopathy, Hypertrophic/genetics , Gene Expression Regulation , Leukocytes, Mononuclear/chemistry , Adult , Aged , Biomarkers/blood , Cardiomyopathy, Hypertrophic/blood , Cardiomyopathy, Hypertrophic/pathology , Case-Control Studies , Female , GATA4 Transcription Factor/blood , GATA4 Transcription Factor/genetics , 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/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/geneticsABSTRACT
Atherosclerosis (ACS) has set off the innovation of molecular markers measured in plasma or serum, and used for the identification of individuals at high risk of Coronary Heart Disease (CHD). In an attempt to improve cardiovascular risk prediction, considerable interest is focused on inflammatory biomarkers including Interleukin (IL)-6, Phospholamban (PLB), Myocyte enhancer factor 2A (MEF2A), and Soluble CD40 ligand. In this paper, signal-processing techniques predicted the characteristic frequencies of the above-mentioned proteins, and common binding sites. The CD40L characteristic frequency, 0.3555+/-0.0001, is correlated with Protease inhibitors and the second peak, 0.4531+/-0.0009, is closely related to Fgfs. This study also revealed that for MEF2A, the characteristic frequency, 0.0488+/-0.0001, is specific for enhancers DNA regulating sequences. The remaining frequencies, 0.3672 +/-0.0001 and 0.4648+/-0.0002, are characteristic of the Myocyte Protease inhibiting activity and SOS operator function. Furthermore, clinical data suggested that the increased levels of CD40L reliably identify the subgroup of patients with ACS who are at highest risk for cardiac events. It is suggested that CD40L is a most prominent candidate for early detection of cardiac disease.
