Novel Monocyte Biomarkers of Atherogenic Conditions

Abstract

Hidden low grade inflammation underlines various cardio-metabolic diseases. This type of inflammation is triggered by abnormal reaction to unwanted self products or deregulation of cellular response to cytokines. In the case of atherosclerosis hidden inflammation is induced by modified lipoproteins and develops under control of different cytokines including IL-4 and TGFβ. The key innate immune cells reacting on these factors are monocytes and macrophages. It is well established that monocytes represent a heterogeneous cell population that easily reacts to pathologic changes in the organism. The best studied marker which expression on monocytes is changed in inflammatory conditions is CD16. Although this marker was shown to be associated with various pathologic conditions its specificity is highly questionable. There is an urgent need of identification of new monocyte-expressed biomarkers that may help not only to detect hidden inflammation but also to determine its type. Our analysis of type 2 activation of human monocytes resulted in identification of 3 novel biomarkers for hidden type 2 inflammation. These include stabilin-1, FOXQ1 and IL17RB. These markers are expressed by monocytes/macrophages under stimulation with IL-4 or its combination with TGFβ - 2 cytokines playing important role in atherogenesis. Stabilin-1 was demonstrated on the monocytes in patients with hyperholisterolemia and in macrophages within atherosclerotic lesions. Association of FoxQ1 and IL17RB with atherosclerosis can be deduced from published data but requires experimental confirmation. Functions of all three proteins suggest that they are not only diagnostic markers, but also involved in atherogenesis and can be used as targets for novel therapeutic approaches.