Genetic insights into atherosclerosis

血液在全身循环，是研究动脉粥样硬化的理想组织。它很容易获得，含有炎症细胞，如单核细胞和T细胞，这是发病的关键因素；循环的血细胞与病变的血管内腔接触，因此可以充当报告者；各种血细胞已经定义了细胞表面标记物，便于其纯化到同质性，用于基因表达分析。

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.