Human coronary heart disease: importance of blood cellular miR-2909 RNomics
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The characterization of atherosclerosis as a chronic inflammatory disease has triggered extensive research worldwide to dissect the pro- and anti-inflammatory, cellular as well as molecular mechanisms governing the pathogenesis of this dreadful disease. Though several microRNAs have been shown to play crucial role in regulating lipid metabolism and inflammation, we are far from resolving the role of epigenomic signals in etiology of coronary heart disease (CHD). The present study was addressed to understand the role of a novel microRNA, miR-2909, in the regulation of genes involved in the initiation and progression of human coronary occlusion. Peripheral blood mononuclear cells were isolated from human CHD subjects at various stages of coronary occlusion (n = 80) and their corresponding normal healthy counterparts (n = 20). Various experimental strategies involving gene expression and silencing, reporter plasmid assays, and flow cytometric analysis were blend together to address the current problem. The present study shows for the first time that the blood cellular miR-2909 expression increases with the severity of coronary occlusion, exhibiting a strong positive correlation (r = 0.943 at p < 0.01). Further, miR-2909 was shown to regulate genes involved in inflammation, immunity, and oxLDL uptake, thereby contributing significantly to the initiation and progression of CHD patho-physiological process. Based upon these results, we propose that miR-2909 RNomics may be a step forward in understanding human CHD at the epigenomic level and can be exploited for designing new therapeutic strategies as well as diagnostic and prognostic markers for this disease in future.
KeywordsmiR-2909 Nuclear factor-κB Kruppel like factor 4 Cylindromatosis T regulatory cells Coronary heart disease subjects
We would like to acknowledge Dr. Anoop Kumar for carrying out immunophenotyping analysis. We also thank W. E. Lowry and K. Plath for the KLF4 expression plasmid and Ms. M. Arora for editing the manuscript, and assistance with KLF4 cloning. This work was supported by Indian Council of Medical Research (ICMR), New Delhi, India.
Conflict of interest
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