Genetic insights into atherosclerosis

动脉粥样硬化的遗传学见解

• 批准号: 8344852
• 负责人: PAUL M. HWANG
• 金额: $ 32.59万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8344852
• 关键词: Arterial Fatty Streak; Atherosclerosis; Blood; Blood Cells; Blood specimen; CCL3 gene; Cell surface; Cells; Cholesterol; Disease; FOS gene; Gene Expression; Gene Expression Profile; Genetic; Genomics; Grant; Homeostasis; Human; Indium; Inflammation; Inflammatory; Legal patent; Mediator of activation protein; Messenger RNA; Metabolic; Mitochondria; Outcome; Oxygen; Pathogenesis; Proteins; Reporter; Reporting; Role; Screening procedure; Severity of illness; T-Lymphocyte; TIS11 protein; Tissue Sample; Tissues; Zinc Fingers; autoimmune arthritis; base; chemokine; human subject; insight; interest; monocyte; novel; osteosarcoma; treatment response

Blood which circulates throughout the body is an ideal tissue for atherosclerosis studies. It is easily accessible and contains inflammatory cells such as monocytes and T cells which are critical elements in pathogenesis; circulating blood cells are in contact with the diseased endovascular lumen and as such may serve as reporters; and the variety of blood cells has defined cell surface markers facilitating their purification to homogeneity for gene expression analysis. Through our studies using human blood and atherosclerotic plaque tissue samples, we have identified the Finkel-Biskis-Jinkins osteosarcoma protooncogene (FOS) as a potential marker of atherosclerosis disease severity and as a potential cholesterol-independent marker of statin treatment. We have recently been granted a use patent for these indications. We are interested in identifying novel mediators of atherosclerosis and have reported that tristetraprolin zinc finger protein 36 (TTP) modulates localized tissue inflammation by directly destabilizing chemokine CCL3 mRNA. This interaction appears to be critical for determining the outcome of inflammatory diseases such as atherosclerosis and autoimmune arthritis. Based on some preliminary observations from our mitochondrial studies, we are examining the role of oxygen homeostasis in modulating inflammation and atherosclerosis.

在全身循环的血液是动脉粥样硬化研究的理想组织。 它易于获取，并含有炎症细胞，如单核细胞和T细胞，这些细胞是发病机制中的关键因素;循环血细胞与患病的血管内管腔接触，因此可用作报告基因;各种血细胞具有明确的细胞表面标志物，有助于将其纯化至同质，以进行基因表达分析。 通过我们使用人类血液和动脉粥样硬化斑块组织样本的研究，我们已经确定了Finkel-Biskis-Jinkins骨肉瘤原癌基因（FOS）作为动脉粥样硬化疾病严重程度的潜在标志物，并作为他汀类药物治疗的潜在胆固醇非依赖性标志物。 我们最近获得了这些适应症的使用专利。 我们有兴趣在确定新的介质动脉粥样硬化，并已报道，tristetraprolin锌指蛋白36（TTP）调节局部组织炎症直接不稳定趋化因子CCL 3 mRNA。 这种相互作用似乎是决定炎症性疾病，如动脉粥样硬化和自身免疫性关节炎的结果至关重要。 基于我们对线粒体研究的一些初步观察，我们正在研究氧稳态在调节炎症和动脉粥样硬化中的作用。