Innate Immunity and Coronary Atherosclerosis Progression: putative cellular and molecular marker.

Purpose. The need for discriminative molecular predictors of CAD presence and progression is widely acknowledged and their clinical utility in preventing CAD-associated adverse events is a matter of debate. Methods. Plaque formation and/or growth were evaluated by CT coronary angiography, comparing two scans at 6 yrs interval. Blood cell transcriptome was analyzed by mRNA sequencing; monocyte subsets and phenotype were quantified by cytometry. Clinical Biochemistry was measured by standard tests. Results. Out of 50 patients enrolled during SMARTool project by FTGM clinical center, 9 are no-CAD patients, 18 showed CAD progression at scan 2, while 23 were unchanged. Clinical characteristics, risk factors and use of statins were similar. Gene analysis together with monocyte characterization showed inflammatory pathways dysregulated and immune response processes activated in CAD progression group. Biological process terms of gene ontology analysis of 50-70 genes evidenced by comparative analysis between progression and no-progression pts groups, reflect inflammation, apoptosis and innate immune cell differentiation. Of these, 5 genes (in the classes of chemokines, interleukins and adhesion molecules) up-regulated significantly (p <0.05) in the progression group. Additionally, the ratio between Mon2/Mon3 indicated an increase in proinflammatory mechanisms in "worsening" CAD respect to stabilization processes. Conclusions. The modulation of genes controlling innate immune system activation is also associated with phenotype changes of blood monocyte subsets These results are unique in the topic of the CAD progression and provide insight into a potential association of the progression of atherosclerosis with innate immunity.