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Early cardiac gene transcript levels in peripheral blood mononuclear cells in patients with untreated essential
Joanna E Kontaraki1, Maria E Marketou, Evangelos A Zacharis
1Molecular Cardiology Laboratory, School of Medicine, University of Crete, and Department of Cardiology, University Hospital of Heraklion, Crete, Greece. kontarak@med.uoc.gr
Insights
Early cardiac gene expression in peripheral blood mononuclear cells (PBMCs) is elevated in hypertension and correlates with blood pressure and left ventricular mass. These findings suggest potential biomarkers for hypertension and cardiac hypertrophy.
Area of Science:
- Cardiovascular Medicine
- Molecular Biology
- Genetics
Background:
- Essential hypertension is linked to cardiac hypertrophy, a process involving complex gene regulation.
- Understanding the molecular mechanisms underlying hypertension-induced cardiac changes is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the expression of early cardiac genes in peripheral blood mononuclear cells (PBMCs) of patients with essential hypertension.
- To explore the relationship between these gene expressions, ambulatory blood pressure monitoring (ABPM) parameters, and echocardiographic left ventricular mass.
Main Methods:
- Quantitative real-time reverse transcription PCR was used to determine gene transcript levels in PBMCs from 62 untreated hypertensive patients and 38 healthy controls.
- Twenty-four-hour ABPM and echocardiography were performed on hypertensive participants.
Main Results:
- Myocardin, GATA4, and Nkx2.5 gene transcripts were significantly upregulated in hypertensive patients compared to controls.
- Transcript levels of myocardin and GATA4 positively correlated with 24-h systolic and mean blood pressure, and pulse pressure.
- Myocardin and GATA4 transcript levels negatively correlated with 24-h BP dipping status and positively correlated with left ventricular mass index.
Conclusions:
- Myocardin and GATA4 transcript levels in PBMCs may serve as potential biomarkers for hypertension, correlating with ABPM parameters.
- Elevated early cardiac gene expression in PBMCs of hypertensive patients is associated with left ventricular mass, suggesting activation of the hypertrophic response gene network.
Objectives:
To assess the expression of early cardiac genes, implicated in the hypertrophic growth response of the adult heart, in peripheral blood mononuclear cells in patients with essential hypertension and its relationship to ambulatory blood pressure monitoring (ABPM) parameters and to echocardiographic left ventricular mass.
Methods:
Twenty-four-hour ABPM, echocardiography and blood sampling were performed in 62 untreated participants with essential hypertension. Blood samples from 38 healthy individuals were included for comparison. Peripheral blood mononuclear cells (PBMCs) were isolated and gene transcript levels were determined by quantitative real-time reverse transcription PCR.
Results:
Myocardin (3.92±0.68 versus 2.09±0.67, P<0.001), GATA4 (3.48±0.68 versus 0.32±0.08, P<0.001) and Nkx2.5 (208.91±35.01 versus 129.75±49.70, P<0.001) were upregulated in hypertensive patients compared with controls. In hypertensive patients, transcript levels of myocardin (r=0.698, P<0.001) and GATA4 (r=0.374, P=0.003) showed significant positive correlations with 24-h systolic blood pressure (BP) as well as with mean BP, (r=0.626, P<0.001) and (r=0.340, P=0.007), respectively. A significant positive correlation between myocardin and 24-h pulse pressure (r=0.467, P<0.001) was also observed. Myocardin (r=-0.606, P<0.001) and GATA4 (r=-0.453, P<0.001) transcript levels also showed significant negative correlations with the mean 24-h dipping status. Additionally, myocardin (r=0.341, P=0.007), GATA4 (r=0.337, P=0.007) and Nkx2.5 (r=0.325, P=0.010) transcript levels showed significant positive correlations with left ventricular mass index.
Conclusion:
Myocardin and GATA4 transcript levels correlate significantly with 24-h ABPM parameters, rendering them potential candidate biomarkers in hypertension. Early cardiac gene transcript levels in PBMCs of hypertensive patients are associated with left ventricular mass and may reflect activation of the hypertrophic response gene network in these patients.
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