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oai:repisalud.isciii.es:20.500.12105/64992024-09-27T07:56:44Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Theodorou, Kosta author van der Vorst, Emiel P. C. author Gijbels, Marion J. author Wolfs, Ine M. J. author Jeurissen, Mike author Theelen, Thomas L. author Sluimer, Judith C. author Wijnands, Erwin author Cleutjens, Jack P. author Li, Yu author Jansen, Yvonne author Weber, Christian author Ludwig, Andreas author Bentzon, Jacob F author Bartsch, Joerg W. author Biessen, Erik A. L. author Donners, Marjo M. P. C. author 2017 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. Sci Rep. 2017; 7(1):11670 10.1038/s41598-017-10549-x 2045-2322 Scientific Reports 28916789 http://hdl.handle.net/20.500.12105/6499 METALLOPROTEASE-DISINTEGRIN ADAM8 TUMOR-NECROSIS-FACTOR MYOCARDIAL-INFARCTION TNF-ALPHA EXPRESSION ANALYSIS PERIPHERAL-BLOOD DENDRITIC CELLS TRANSGENIC MICE IMMUNE-SYSTEM MACROPHAGES Whole body and hematopoietic ADAM8 deficiency does not influence advanced atherosclerotic lesion development, despite its association with human plaque progression