Elevated expression of the interleukin-8 receptors CXCR1 and CXCR2 in peripheral blood cells in obstructive coronary artery disease

Objectives: As accumulation of monocytes and macrophages is a feature of atherosclerotic plaque at all stages, inflammatory gene expression profiling of peripheral blood mononuclear cells may provide a more reliable measure of atherogenesis than systemic inflammatory markers. The aim of this study was to determine whether expression patterns of inflammatory regulators in blood are correlated with severity and progression of coronary artery disease. Methods: PCR expression arrays were used to profile mRNA levels of 84 candidate genes in blood from three patients with persistent perfusion defects, three with improved perfusion, and two without perfusion defects as measured by serial PET myocardial perfusion imaging. A case-control study compared expression of inflammatory genes in 25 patients with stress-induced perfusion defects and 25 controls using quantitative real-time PCR. Results: Expression array analysis identified IL-8, CXCR1, and CXCR2 as genes showing increased expression in patients with persistent perfusion defects. The case-control study confirmed a significant increase in CXCR1 (P=0.04) and CXCR2 (P=0.002) mRNAs in blood in males with obstructive CAD, but not in females. There was no difference in IL-8 mRNA level between cases and controls (P=0.1). Coordinated expression of CXCR1 and CXCR2 mRNA was more pronounced in controls (r=0.96) than in patients with perfusion defects (r=0.73). Conclusions: mRNA levels for CXCR1 and CXCR2 are increased in blood in males with obstructive CAD and decreased in patients with improved perfusion, suggesting that these genes may serve as markers of disease severity and progression.