Genomic Analysis of Circulating Cells: A Window Into Atherosclerosis

Translational studies using genomic techniques in cardiovascular diseases are still in their infancy. Access to disease-associated cardiovascular tissues from patients has been a major impediment to progress in contrast to the diagnostic advances made by oncologists using gene expression on readily available tumor samples. Nonetheless, progress is being made for atherosclerosis by carefully designed experiments utilizing diseased tissue or surrogate specimens. This review details the rationale and findings of a study utilizing freshly isolated blood mononuclear cells from patients undergoing carotid endarterectomy due to atherosclerotic stenosis and from matched healthy subjects. By querying this cardiovascular tissue surrogate, the messenger RNA levels of the Finkel–Biskis–Jenkins osteosarcoma gene in circulating monocytes were found to correlate with atherosclerosis severity in patients and with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy in healthy subjects. The major finding of this investigation is discussed in relation to observations from other human atherosclerosis gene expression studies. These distinct studies converge to demonstrate the unequivocal importance of inflammation in atherosclerosis. Although the clinical utility of the specific findings remains open, the identification of similar genes by different investigations serves to validate our report. They also provide us with insights into pathogenesis that may impact future translational applications.