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Titel: Elevated expression of the metalloproteinase ADAM8 associates with vascular diseases in mice and humans
VerfasserIn: Schick, Daniel
Babendreyer, Aaron
Wozniak, Justyna
Awan, Tanzeela
Noels, Heidi
Liehn, Elisa
Bartsch, Jörg-W.
Vlacil, Ann-Kathrin
Grote, Karsten
Zayat, Rashad
Goetzenich, Andreas
Ludwig, Andreas
Dreymueller, Daniela
Sprache: Englisch
Titel: Atherosclerosis
Bandnummer: 286
Seiten: 163-171
Verlag/Plattform: Elsevier
Erscheinungsjahr: 2019
Freie Schlagwörter: Metalloproteinase
Endothelial cells
Leukocytes
Atherosclerosis
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Background and aims Members of the family of a disintegrin and metalloproteinases (ADAMs) and their substrates have been previously shown to modulate the inflammatory response in cardiac diseases, but studies investigating the relevance of ADAM8 are still rare. Our aim is to provide evidence for the inflammatory dysregulation of ADAM8 in vascular diseases and its association with disease severity. Methods Western-type diet fed Apoe−/− and Ldlr−/− mice and artery ligation served as murine model for atherosclerosis and myocardial infarction, respectively. Human bypass grafts were used to study the association with coronary artery disease (CAD), with the simplified acute physiology score II (SAPS II) as a measure of postoperative organ dysfunction. Human primary vascular and blood cells were analyzed under basal and inflammatory conditions. mRNA levels were determined by RT-qPCR, ADAM8 protein levels by ELISA, immunohistochemistry or flow cytometry. Results ADAM8/ADAM8 expression is associated with atherosclerosis and CAD such as myocardial infarction in both mice and humans, especially in endothelial cells and leukocytes. We observed a strong in vivo and in vitro correlation of ADAM8 with the vascular disease markers VCAM-1, ICAM-1, TNF, IL-6, and CCL-2. Serum analysis revealed a significant elevation of soluble ADAM8 serum levels correlating with soluble CXCL16 levels and SAPS II. Conclusions We demonstrate a general association of ADAM8 with cardiovascular diseases in mice and humans predominantly acting in endothelial cells and leukocytes. The correlation with postoperative organ dysfunctions in CAD patients highlights the value of further studies investigating the specific function of ADAM8 in cardiovascular diseases.
DOI der Erstveröffentlichung: 10.1016/j.atherosclerosis.2019.03.008
URL der Erstveröffentlichung: https://www.sciencedirect.com/science/article/abs/pii/S0021915019301376
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-371715
hdl:20.500.11880/33727
http://dx.doi.org/10.22028/D291-37171
ISSN: 0021-9150
Datum des Eintrags: 7-Sep-2022
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Experimentelle und Klinische Pharmakologie und Toxikologie
Professur: M - Jun.-Prof. Dr. Daniela Yildiz
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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