Mechanisms and markers of vascular damage in ANCA-associated vasculitis.
Much progress has been made in understanding the pathogenesis of anti-neutrophil cytoplasmic antibodies (ANCA)-associated small-vessel vasculitis and interaction between ANCA and micro-vascular endothelial cells are centre stage. The interactions of these key players culminate in respiratory burst of the neutrophil with release of radicals and proteases and subsequent endothelial cell and tissue damage. During the last decade, markers have become available to assess the extent and/or acuity of vascular damage in a clinical setting. First, circulating endothelial cells (CEC) have emerged as reliable surrogate markers of endothelial damage in vasculitis. More recently, endothelial microparticles have been used and appear to reflect damage and activation of the cells. Data on endothelial progenitor cells in vasculitis are sparse but intriguing while a genuine progenitor cell deficiency remains controversial. The severely damaged phenotype of CEC in vasculitis led to the hypothesis that such circulating apoptotic and/or necrotic debris may itself be a mediator of disease and first data from experimental studies have added proof to this assumption. Such effects may well contribute to a pro-inflammatory environment in ANCA-associated small-vessel vasculitis and in vascular disease in general. Here, we review mechanisms and markers of endothelial damage and repair in ANCA-associated vasculitis and put these findings into perspective.
Division of Nephrology, Department of Medicine, Hannover Medical School, Hannover, Germany. haubitz.marion@mh-hannover.de
Marion
M
Haubitz
Ajay
A
Dhaygude
Alexander
A
Woywodt
D000818:Animals; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D015415:Biomarkers; D001808:Blood Vessels / Q000276:immunology* / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D019700:Thrombospondin 1 / Q000276:immunology / Q000378:metabolism
D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; D019700:Thrombospondin 1