Abstract 16752: Peripheral Blood Monocytes and Dendritic Cells of Patients with Peripheral Artery Occlusive Disease Show a Proinflammatory Phenotype and Increased Production of Reactive Oxygen Species in Dependence of Diabetes Mellitus and their Clinical Status
Background: Monocytes and dendritic cells (DC) are crucial for regulating the immune system in chronic inflammatory processes, like atherosclerosis. Both are present in atherosclerotic lesions, where reactive oxygen species (ROS) are produced. All directly influence and aggravate atherosclerosis. In the present study, we performed an in vivo analysis and phenotypic characterization of peripheral blood monocytes and DC of patients with peripheral artery occlusive disease (AOD) with different status of the disease (State II a/b — IV) and investigated the production of ROS in comparison to healthy individuals.
Methods: Peripheral blood leucocytes of 25 patients and controls were analyzed from whole blood by flow cytometry (FACS-Canto, BD Biosciences). Monocytes and DC were identified in relation to size, granulation and surface molecules and analyzed for CD14, CD16, MDC8 on monocytes, CD86, CD40, CD83 on DC. ROS formation from leucocytes was determined by chemiluminescence assays in whole blood and serum antioxidant capacity was measured by DPPH-Assay.
Results: Peripheral AOD patients showed a significant higher proportion of proinflammatory CD14-CD16+ monocytes and MDC8 positive monocytes (p<0.01). Patients had more myeloid (mDC), and less plasmacytoid DCs (pDC), changing the mDC/pDC ratio in favor of mDCs (p<0.05). mDC had a significantly increased expression of CD40 and CD86 (p<0.05). Peripheral AOD patients showed a reduced antioxidant capacity and increased ROS production. Among these, patients with a longer walking distance (over 200 m) showed a lower ROS production and increased antioxidant capacity in contrast to patients with shorter walking distance (below 200m) (p<0.05). Diabetic patients presented a further reduced antioxidative capacity and increased ROS production (p<0.05).
Conclusions: Peripheral blood monocytes and DC of AOD patients display a proinflammatory phenotype, increased production of ROS and reduced antioxidant capacity. The better the walking distance, the lower the amount of ROS production and the higher the antioxidant capacity. These in vivo insights in the process of atherogenesis suggest an amelioration of the disease by antioxidant, antiinflammatory strategies such as intensive exercise.
- © 2010 by American Heart Association, Inc.