Abstract 3031: Enhanced Vascular Inflammation In Aortic Valve Stenosis Induced By Increased Proinflammatory Microparticles
Background Aortic valve stenosis (AVS) is one of the most important cardiac valve diseases whereas the mechanisms of its progression are still unknown. However, the involvement of mononuclear cells and of chronic systemic inflammation has been suggested by histological analysis. Microparticles (MP) are cell vesicles that are released from eukaryotic cells in case of cell activation and represent the state of activation of the cell of origin. We hypothesize that shear stress caused by the constricted aortic orifice contributes to systemic proinflammation through activation of circulating blood cells and subsequent generation of MPs.
Methods + Results Circulating MPs from platelet- (PMPs: CD31+/CD61+ or CD62P+), leukocyte- (LMPs: CD11b+) and endothelial cell- (EMPs: CD62E+) origin were measured by flow cytometry in 22 patients with severe AVS and compared with 18 controls. Besides the AVS both groups had similar baseline characteristics. We found that PMPs (AVS: 868±600 cpm vs. co: 504±230 cpm, p=0.046), particularly CD62P+ PMPs (AVS: 76.0±44.5 cpm vs. co: 47.8±21.8 cpm, p= 0.028), which play an important role in platelet-leukocyte interaction, were increased in AVS patients. Consequently, AVS patients had more activated monocytes (CD11b+) compared with controls (AVS: 902.36±330.72 MFI vs. co: 675.71±189.49 MFI; p=0.042), an observation that was also reflected by increased numbers of LMPs (AVS: 31.6±18.5 cpm vs. co: 19.4±9.7 cpm, p=0.014). Furthermore EMPs were increased in AVS patients (AVS: 19.7±12.3 cpm vs. co: 10.4±6.8 cpm, p=0.008). These particles reflect the activation of endothelial cells and confer systemic proinflammatory activity. We found a strong correlation between activated monocytes and EMPs suggesting that activated monocytes cause endothelial cell activation and thereby EMP release.
Conclusion AVS is accompanied by increased levels of MPs. We suggest a ‘vicious circle’ in aortic valve disease: Increased shear forces induce the generation of PMPs that activate monocytes and LMPs. Subsequently, LMPs and activated monocytes cause a systemic vascular proinflammatory state resulting in activation of endothelial cells and release of CD62E+ EMPs. This systemic proinflammation contributes to the progression of valvular disease.