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Elucidating the Histone Deacetylase Gene Expression Signatures in Peripheral Blood Mononuclear Cells That Correlate
K Monisha1, S Mahema1, M Chokkalingam2
1Drug Discovery and Multi-omics Laboratory, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Chettinad Hospital and Research Institute, Kelambakkam 603103, India.
Insights
Histone deacetylases (HDACs) gene expression is linked to cardiovascular function in coronary artery disease (CAD). Specific HDAC profiles can help classify CAD patients, offering potential for new diagnostic methods.
Area of Science:
- Epigenetics
- Cardiovascular Disease Research
- Molecular Biology
Background:
- Histone deacetylases (HDACs) are implicated in atherosclerosis pathogenesis.
- The role of HDACs in coronary artery disease (CAD) clinical and cardiovascular function remains largely unknown.
- HDACs represent emerging epigenetic diagnostic biomarkers.
Purpose of the Study:
- To profile the gene expression of HDAC1-11 in peripheral blood mononuclear cells of CAD patients.
- To evaluate the influence of HDAC gene expression on hematological, biochemical, and echocardiographic indices in CAD.
- To develop a diagnostic model for classifying CAD based on HDAC profiles.
Main Methods:
- Gene expression profiling of HDAC1-11 in 62 CAD patients and 62 healthy controls.
- Analysis of associations between HDAC expression and hematological, biochemical, and echocardiographic parameters.
- Construction of a diagnostic model using key HDACs for CAD classification.
Main Results:
- Upregulation of HDACs 1, 2, 4, 6, 8, 9, and 11, and downregulation of HDAC3 were observed in CAD patients.
- Significant correlations were found between specific HDAC expression levels and hematological, biochemical (LDL, HDL, TGL), and echocardiographic parameters (LVEF, GLS, MV E/A, IVRT, PV S/D).
- A diagnostic model incorporating crucial HDACs achieved 88.6% accuracy in classifying CAD patients from controls.
Conclusions:
- HDAC gene expression is associated with cardiac function in CAD.
- Specific HDAC profiles offer insights into CAD pathogenesis and cardiovascular status.
- This study provides a foundation for developing novel molecular diagnostic methods for CAD.
Abstract:
A proinflammatory role of HDACs has been implicated in the pathogenesis of atherosclerosis as an emerging novel epigenetic diagnostic biomarker. However, its association with the clinical and cardiovascular function in coronary artery disease is largely unknown. The study aimed to profile the gene expression of HDAC1-11 in human peripheral blood mononuclear cells and to evaluate their influence on hematological, biochemical, and two-dimensional echocardiographic indices in CAD. The HDAC gene expression profiles were assessed in 62 angioproven CAD patients and compared with 62 healthy controls. Among the HDACs, upregulated HDACs 1,2, 4, 6, 8, 9, and 11 were upregulated, and HDAC3 was downregulated, which was significantly (p ≤ 0.05) linked with the hematological (basophils, lymphocytes, monocytes, and neutrophils), biochemical (LDL, HDL, and TGL), and echocardiographic parameters (cardiac function: biplane LVEF, GLS, MV E/A, IVRT, and PV S/D) in CAD. Furthermore, our constructed diagnostic model with the crucial HDACs establishes the most crucial HDACs in the classification of CAD from control with an excellent accuracy of 88.6%. Conclusively, our study has provided a novel perspective on the HDAC gene expression underlying cardiac function that is useful in developing molecular methods for CAD diagnosis.
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