Genetic insights into atherosclerosis

点击翻译按钮获取中文摘要

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.