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Gene expression of thrombomodulin, TNF-α and NF-KB in coronary artery disease patients of Pakistan

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Abstract

Thrombomodulin (THBD) is an endothelial surface glycoprotein receptor, having a pivotal role in maintaining laminar blood flow. It functions to protect endothelial integrity by exhibiting anti-coagulation and anti-inflammatory properties thereby playing a key role in cardiovascular disease (CVD) pathology. Cholesterol lowering drugs have shown to alter the anti-inflammatory effects of cytokines. Understanding the molecular aspects of THBD gene and its relation to inflammatory cytokines is important to identify new prognostic and therapeutic targets for the CVD treatments. The present study was conducted to measure the expression of THBD, TNF-α and NF-kB genes in coronary artery disease patients (CAD) in Pakistani population. Lipid profile and BMI was compared both on fifty CAD patients and fifty healthy individuals. Expression analysis for THBD, TNF-α and NF-kB was carried out using real time PCR. The effect of lipid lowering drugs on cardiometabolic risk variables especially gene expression was analyzed. Our results indicated that the difference in BMI was marginal; however LDL-cholesterol and triglycerides levels in CAD patients were significantly higher than healthy individuals. THBD gene was significantly up-regulated whereas TNF-α and NF-kB were significantly down regulated in CAD individuals. Further exploration revealed that these variations were accounted to the use of statins by the patients. The use of statins by CAD patients up-regulated the mRNA expression of THBD by down-regulation of inflammatory mediators. The enhanced expression of endothelial THBD in response to cholesterol lowering drugs establishes a novel pleiotropic target that can be of clinical significance in thromboembolic and inflammatory disorders.

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Funding

This work was supported by COMSATS University Islamabad and Shifa Tameer-e-Millat University, Islamabad.

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Authors and Affiliations

  1. Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad, 45550, Pakistan

    Muhammad Rafiq & Muhammad Jawad Khan

  2. Shifa College of Medicine, Shifa Tameer-E-Millat University, Islamabad, 45550, Pakistan

    Muhammad Rafiq, Afrose Liaquat, Nadia Saeed & Sana Mumtaz

  3. Armed Forces Bone Marrow Transplant Centre, Rawalpindi, 46000, Pakistan

    Ghassan Umair Shamshad

  4. Department of Psychosomatic Medicine and Psychotherapy, University Medical Center, 37075, Gottingen, Germany

    Sana Mumtaz

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  1. Muhammad Rafiq
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Contributions

MR. was involved in Conceptualization, Methodology, Investigation, Formal analysis, Writing—Original Draft. AL. contributed in Conceptualization, Validation, Resources, Writing—Review & Editing, Project administration, Funding acquisition, Supervision. NS. and GUS. contributed through Resources, Investigation and Visualization. SM was involved in Conceptualization, Methodology and Investigation. MJK contributed in Conceptualization, Validation, Resources, Formal analysis, Writing—Review & Editing, Project administration, Funding acquisition, Supervision.

Corresponding authors

Correspondence to Afrose Liaquat or Muhammad Jawad Khan.

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The authors declare that they have no conflict of interest.

Ethical approval

The study has been approved by the institutional and ethical review board of Shifa Tameer-e-Millat University (IRB # 016–506-2019) and COMSATS University Islamabad. The present study was approved by Ethics and IRB committee.

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Written informed consent was taken from all the participants. Consent for publication was taken from all the authors.

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Rafiq, M., Liaquat, A., Saeed, N. et al. Gene expression of thrombomodulin, TNF-α and NF-KB in coronary artery disease patients of Pakistan. Mol Biol Rep 47, 7575–7582 (2020). https://doi.org/10.1007/s11033-020-05824-6

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  • DOI: https://doi.org/10.1007/s11033-020-05824-6

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