Neutrophil Activation In Coronary Artery Ectasia

BACKGROUND AND PURPOSE:Coronary artery ectasia(CAE)is defined as the abnormal dilation of coronary arteries.Neutrophil activation may contribute to the development of CAE.After activation,neutrophil granules are mobilized and secrete various products,including proteases,myeloperoxidase(MPO)and other proteins.Plasma levels of neutrophil serine proteases are elevated in CAE patients,which may destruct vascular walls and cause ectasia.Decreased intracellular MPO level as well as increased extracellular MPO level are recognized as markers of neutrophil activation.Neutrophil Extracellular Traps(NETs)is the remnant that neutrophil left after the degranulation process.The first aim of this study was to determine the activation status of circulating neutrophils in CAE patients.The second aim was to determine the main causes of this phenomena.The last one was to clarify the relation between NETs and CAE.METHODS:In part one,peripheral blood samples of subjects were collected after angiography,61 patients of which were with coronary artery ectasia(CAE),82 patients were with coronary artery disease(CAD)and 75 subjects were with normal coronary arteries(CON).Additionally,30 patients of each groups were enrolled in Part two and three.We measured the intra-neutrophil mean MPO index(MPXI)using the flow cytochemistry complete blood analyzer(ADVIA2120).The plasma MPO concentration was measured using enzyme-linked immunosorbent assay(ELISA).In part two and three,The plasma adhesion molecule levels,ANCA and AECA antigen levels,cytokine levels,secretory leucocyte protease inhibitor concentration and NETs concentration were measured using ELISA.Additionally,the dsDNA level was estimated by PicoGreen as a representative for NETs.RESULTS:MPXI was comparatively decreased in CAE patients.CAE group had significant higher plasma MPO level,compared to CAD and CON groups.MPXI was inversely correlated with plasma MPO level.CAE patients had higher plasma adhesion molecule level and IL1? might contribute to the neutrophil activation phenomenon.In addition,the NETs concentration was high in CAE group.CONCLUSION:This study is the first to measure intracellular and extracellular levels of MPO to confirm the activation status of neutrophils in CAE patients.Peripheral neutrophils are activated and then various contents and NETs are released into plasma,which may exacerbate vascular wall degeneration.The underlying causative factors of neutrophil activation may include IL1?.