Dendritic cells and vascular inflammation in patients with coronary artery disease with and without chronic kidney disease

Objective: Dendritic cells (DCs) are priming local immune responses, and their tissue-associated activity increases in inflammatory conditions. In patients with coronary artery disease (CAD), circulating dendritic cell precursors (DCPs) are reduced. This study investigates circulating DCPs and tissue densities of migrated DCs in CAD patients undergoing bypass surgery, focussing on patients with chronic kidney disease (CKD) as a risk factor for CAD and a condition of chronic vascular inflammation. Approach and Results: Circulating DCPs were measured in the peripheral blood (before surgery) using fluorescence-activated cell sorting (FACS) in n=59 patients and results were compared with an age-matched healthy control group (n=45). DCs were stained (Fascin) in circular sections of the internal thoracic artery taken during bypass surgery and mature (CD83+) and immature (CD209+) DCs were differentiated. Cell densities were obtained digitally. Descriptive statistics and correlation analysis generated hypotheses. Circulating myeloid DCPs were reduced (p<0.001), concomitant CKD added no further reduction. Immature DCs were predominantly detected in the adventitia, mature DCs dominated in the intima (p<0.001). In CKD, reduced circulating myeloid DCPs correlated with immature DCs in the vessel wall (r=0.87; p=0.002) and rather mature DCs were detectable; in patients without CKD immature DCs were dominating. C-reactive protein correlated with mature DCs (r=0.38; p=0.026). Conclusions: Quantities of DCPs and mature and immature DCs vary between the vessel wall layers. The dominance of immature myeloid DCs in the adventitia suggests activation of the vascular-associated lymphoid tissue (VALT). Intensified inflammation associated with CKD may have promoted the maturation of myeloic DCs.