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Thromb Haemost 2018; 118(07): 1167-1175
DOI: 10.1055/s-0038-1660479
Review Article
Georg Thieme Verlag KG Stuttgart · New York

A Disintegrin and Metalloproteases (ADAMs) in Cardiovascular, Metabolic and Inflammatory Diseases: Aspects for Theranostic Approaches

Emiel P. C. van der Vorst
1   Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
2   Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany
,
Christian Weber
1   Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
2   Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany
3   DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
,
Marjo M. P. C. Donners
1   Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
› Author Affiliations Funding This work was supported by the Alexander von Humboldt Foundation to E.P.C.v.d.V., by the Deutsche Forschungsgemeinschaft (SFB 1123-A1), the German Centre for Cardiovascular Research (MHA VD 1.2), the European Research Council (ERC AdG °249929), the German Federal Ministry of Education and Research (grant number 01KU1213A), the Leducq Transatlantic Network CVGene(Fx) to C.W. and by the Netherlands Heart Foundation (Dr. E. Dekker grant 2012T079) to M.M.P.C.D.
Further Information

Publication History

09 February 2018

02 May 2018

Publication Date:
06 June 2018 (online)

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Abstract

A disintegrin and metalloproteases (ADAMs) are membrane-bound enzymes responsible for the shedding or cleavage of various cell surface molecules, such as adhesion molecules, cytokines/chemokines and growth factors. This shedding can result in the release of soluble proteins that can exert agonistic or antagonistic functions. Additionally, ADAM-mediated cleavage can render these membrane proteins inactive. This review will describe the role and association of ADAMs in various pathologies with a main focus on ADAM10 and ADAM17 in atherosclerosis, including a brief overview of atherosclerosis-related ADAM substrates. Furthermore, ADAMs involvement in other metabolic and inflammatory diseases like diabetes, sepsis, Alzheimer's disease and rheumatoid arthritis will be highlighted. Subsequently, we will briefly discuss an interesting emerging field of research, i.e. the potential implications of ADAM expression in extracellular vesicles. Finally, several ADAM-based therapeutic and diagnostic (theranostic) opportunities will be discussed, while focusing on key questions about the required specificity and selectivity.

Keywords

a disintegrin and metalloprotease - pathologies - cardiovascular disease - atherosclerosis - therapy

Note: The review process for this paper was fully handled by Gregory Y. H. Lip, Editor-in-Chief.


 

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