Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/6499
Whole body and hematopoietic ADAM8 deficiency does not influence advanced atherosclerotic lesion development, despite its association with human plaque progression
Theodorou, Kosta | van der Vorst, Emiel P. C. | Gijbels, Marion J. | Wolfs, Ine M. J. | Jeurissen, Mike | Theelen, Thomas L. | Sluimer, Judith C. | Wijnands, Erwin | Cleutjens, Jack P. | Li, Yu | Jansen, Yvonne | Weber, Christian | Ludwig, Andreas | Bentzon, Jacob F CNIC | Bartsch, Joerg W. | Biessen, Erik A. L. | Donners, Marjo M. P. C.
Sci Rep. 2017; 7(1):11670
Although A Disintegrin And Metalloproteinase 8 (ADAM8) is not crucial for tissue development and homeostasis, it has been implicated in various inflammatory diseases by regulating processes like immune cell recruitment and activation. ADAM8 expression has been associated with human atherosclerosis development and myocardial infarction, however a causal role of ADAM8 in atherosclerosis has not been investigated thus far. In this study, we examined the expression of ADAM8 in early and progressed human atherosclerotic lesions, in which ADAM8 was significantly upregulated in vulnerable lesions. In addition, ADAM8 expression was most prominent in the shoulder region of human atherosclerotic lesions, characterized by the abundance of foam cells. In mice, Adam8 was highly expressed in circulating neutrophils and in macrophages. Moreover, ADAM8 deficient mouse macrophages displayed reduced secretion of inflammatory mediators. Remarkably, however, neither hematopoietic nor whole-body ADAM8 deficiency in mice affected atherosclerotic lesion size. Additionally, except for an increase in granulocyte content in plaques of ADAM8 deficient mice, lesion morphology was unaffected. Taken together, whole body and hematopoietic ADAM8 does not contribute to advanced atherosclerotic plaque development, at least in female mice, although its expression might still be valuable as a diagnostic/ prognostic biomarker to distinguish between stable and unstable lesions.
METALLOPROTEASE-DISINTEGRIN ADAM8 | TUMOR-NECROSIS-FACTOR | MYOCARDIAL-INFARCTION | TNF-ALPHA | EXPRESSION ANALYSIS | PERIPHERAL-BLOOD | DENDRITIC CELLS | TRANSGENIC MICE | IMMUNE-SYSTEM | MACROPHAGES