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Gene expression of thrombomodulin, TNF-α and NF-KB in coronary artery disease patients of Pakistan.
Molecular Biology Reports ( IF 2.6 ) Pub Date : 2020-09-15 , DOI: 10.1007/s11033-020-05824-6
Muhammad Rafiq 1, 2 , Afrose Liaquat 2 , Nadia Saeed 2 , Ghassan Umair Shamshad 3 , Sana Mumtaz 2, 4 , Muhammad Jawad Khan 1
Affiliation  

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.



中文翻译:

巴基斯坦冠心病患者血栓调节蛋白,TNF-α和NF-KB的基因表达

血栓调节蛋白(THBD)是一种内皮表面糖蛋白受体,在维持层流中起关键作用。它通过表现出抗凝和抗炎特性来保护内皮的完整性,从而在心血管疾病(CVD)病理中起关键作用。降低胆固醇的药物已显示出可改变细胞因子的抗炎作用。了解THBD基因的分子方面及其与炎性细胞因子的关系对于确定CVD治疗的新预后和治疗目标非常重要。本研究旨在测定THBDTNF - α和NF-kB的表达。巴基斯坦人群冠心病患者(CAD)中的基因。比较了50例CAD患者和50例健康个体的血脂谱和BMI。使用实时PCR进行THBDTNF - α和NF-kB的表达分析。分析了降脂药物对心脏代谢风险变量尤其是基因表达的影响。我们的结果表明,BMI的差异很小。然而,CAD患者中的LDL-胆固醇和甘油三酯水平显着高于健康个体。THBD基因显着上调,而TNF - α和NF-kB在CAD个体中显着下调。进一步的探索表明,这些差异与患者使用他汀类药物有关。CAD患者使用他汀类药物可通过下调炎症介质来上调THBD的mRNA表达。响应于降低胆固醇的药物,内皮THBD的表达增强,建立了一种新型的多效靶标,在血栓栓塞性和炎性疾病中可能具有临床意义。

更新日期:2020-09-15
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