Phenotyping of circulating monocytes in coronary artery diseases
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Abstract
Coronary artery disease (CAD) which is characterized by atherosclerosis in coronary artery becomes the single leading cause of death worldwide. Non-alcoholic fatty liver disease (NAFLD) has been identified as an independent risk factor for CAD. CAD patients display different outcomes over long-term follow-up, and gender disparities in CAD prevalence. Although CAD has been extensively studied, key pathways involved in the pathogenesis are not thoroughly understood. As main component of the innate immune system, monocytes play major roles in pathogenesis of NAFLD and CAD. Therefore, our study focused on the phenotyping of circulating monocytes.
In the first part, the circulating monocyte phenome in NAFLD was conducted to investigate the association between NAFLD and alteration in circulating monocyte subsets. It was demonstrated that total monocyte fraction and non-classical monocyte fraction were increased and defined independently risk for NAFLD. The non-classical monocyte fraction and classical monocyte fraction were strongly associated with waist-to-hip ratio (WHR). In the second part, the whole genome expression profiling was performed to identify key genes expressed on monocytes associated with clinical outcomes and gender differences of CAD. Firstly, there were no signifiant differentially expressed genes on monocytes associated with clinical outcomes and gender differences of CAD. Secondly, 20 candidate gens including PPBP, CD69, CCL2, EMP1, SMAD7, THBD, TNFRSF12A, ID1, CD226, CCL5, CTSL1, SDC4, NAB2, PIM1, FFAR3, LDLR, CCR1, MAPK14, UBR2, OGT were differently expressed in CAD patients compared to healthy controls. Most candidates identified were associated with inflammatory response and lipid metabolism. They were needed further validation.
In conclusion, these data show that circulating monocytes are indicative a dysmetabolic and inflammatory state in humans, and inflammatory pathway is important for the pathogenesis of CAD.
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DFG Project uulm
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CAD, Coronary artery disease, NAFLD, Phenotyping, Subsets, Koronare Herzkrankheit, Monocytes, Non-alcoholic fatty liver disease, DDC 610 / Medicine & health