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Dysregulated expression of STAT1, miR-150, and miR-223 in peripheral blood mononuclear cells of coronary artery disease patients with significant or insignificant stenosis
Authors:Zahra Saadatian  Ziba Nariman-Saleh-Fam  Milad Bastami  Yasser Mansoori  Isa Khaheshi  Saeed Alipour Parsa  Abdolreza Daraei  Sepideh Zununi Vahed  Bahman Yousefi  Hossein Samadi Kafil  Shirin Eyvazi  Sayyed Mohammad Hossein Ghaderian  Mir Davood Omrani
Institution:1. Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran;2. Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;3. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran;4. Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran;5. Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran;6. Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran;7. Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;8. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;9. Department of Biotechnology, School of Advanced Technology in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract:Coronary artery disease (CAD) is a multicellular disease characterized by chronic inflammation. Peripheral blood-mononuclear cells (PBMCs), as a critical component of immune system, actively cross-talk with pathophysiological conditions induced by endothelial cell injury, reflecting in perturbed PBMC expression. STAT1 is believed to be relevant to CAD pathogenesis through regulating key inflammatory processes and modulating STAT1 expression play key roles in fine-tuning CAD-related inflammatory processes. This study evaluated PBMC expressions of STAT1, and its regulators (miR-150 and miR-223) in a cohort including 72 patients with CAD with significant ( ≥ 50%) stenosis, 30 patients with insignificant ( < 50%) coronary stenosis (ICAD), and 74 healthy controls, and assessed potential of PBMC expressions to discriminate between patients and controls. We designed quantitative real-time polymerase chain reaction (RT-qPCR) assays and identified stable reference genes for normalizing PBMC quantities of miR-150, miR-223, and STAT1 applying geNorm algorithm to six small RNAs and five mRNAs. There was no significant difference between CAD and ICAD patients regarding STAT1 expression. However, both groups of patients had higher levels of STAT1 than healthy controls. miR-150 and miR-223 were differently expressed across three groups of subjects and were downregulated in patients compared with healthy controls, with the lowest expression levels being observed in patients with ICAD. ROC curves suggested that PBMC expressions may separate between different groups of study subjects. PBMC expressions also discriminated different clinical manifestations of CAD from ICADs or healthy controls. In conclusion, the present study reported PBMC dysregulations of STAT1, miR-150, and miR-223, in patients with significant or insignificant coronary stenosis and suggested that these changes may have diagnostic implications.
Keywords:coronary artery disease  microRNA  miR-150  miR-223  PBMC  peripheral blood mononuclear cell  STAT1
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