A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase
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Published:2023-06-09
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Ragavan Vinitha N.ORCID, Nair Pramod C.ORCID, Jarzebska Natalia, Angom Ramcharan SinghORCID, Ruta Luana, Bianconi ElisaORCID, Grottelli Silvia, Tararova Natalia D., Ryazanskiy Daniel, Lentz Steven R., Tommasi Sara, Martens-Lobenhoffer JensORCID, Suzuki-Yamamoto Toshiko, Kimoto Masumi, Rubets Elena, Chau Sarah, Chen Yingjie, Hu XinliORCID, Bernhardt NadineORCID, Spieth Peter M., Weiss Norbert, Bornstein Stefan R., Mukhopadhyay DebabrataORCID, Bode-Böger Stefanie M., Maas RenkeORCID, Wang YingORCID, Macchiarulo Antonio, Mangoni Arduino A., Cellini Barbara, Rodionov Roman N.ORCID
Abstract
AbstractDimethylarginine dimethylaminohydrolase 1 (DDAH1) protects against cardiovascular disease by metabolising the risk factor asymmetric dimethylarginine (ADMA). However, the question whether the second DDAH isoform, DDAH2, directly metabolises ADMA has remained unanswered. Consequently, it is still unclear if DDAH2 may be a potential target for ADMA-lowering therapies or if drug development efforts should focus on DDAH2’s known physiological functions in mitochondrial fission, angiogenesis, vascular remodelling, insulin secretion, and immune responses. Here, an international consortium of research groups set out to address this question using in silico, in vitro, cell culture, and murine models. The findings uniformly demonstrate that DDAH2 is incapable of metabolising ADMA, thus resolving a 20-year controversy and providing a starting point for the investigation of alternative, ADMA-independent functions of DDAH2.
Funder
Deutsche Stiftung für Herzforschung Deutscher Akademischer Austauschdienst U.S. Department of Health & Human Services | National Institutes of Health
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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