A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase

Ragavan VN, Nair PC, Jarzebska N, Angom RS, Ruta L, Bianconi E, Grottelli S, Tararova ND, Ryazanskiy D, Lentz SR, Tommasi S, Martens-Lobenhoffer J, Suzuki-Yamamoto T, Kimoto M, Rubets E, Chau S, Chen Y, Hu X, Bernhardt N, Spieth PM, Weiss N, Bornstein SR, Mukhopadhyay D, Bode-Böger SM, Maas R, Wang Y, Macchiarulo A, Mangoni AA, Cellini B, Rodionov RN (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 14

Article Number: 3392

Journal Issue: 1

DOI: 10.1038/s41467-023-38467-9

Abstract

Dimethylarginine 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.

Authors with CRIS profile

Renke Maas Professur für Arzneimitteltherapiesicherheit und Klinische Pharmakologie

Additional Organisation(s)

FAU Forschungszentrum Neue Wirkstoffe (FAU NeW)

Involved external institutions

Flinders Medical Centre AU Australia (AU) Technische Universität Dresden DE Germany (DE) Università degli Studi di Perugia IT Italy (IT) Mayo Clinic Hospital US United States (USA) (US) University of Iowa US United States (USA) (US) Okayama Prefectural University / 岡山県立大学 JP Japan (JP) Mayo Clinic College of Medicine and Science (MCCMS) US United States (USA) (US) Otto-von-Guericke-Universität Magdeburg DE Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden DE Germany (DE) Peking University (PKU) / 北京大学 CN China (CN) University of Mississippi Medical Center US United States (USA) (US)

How to cite

APA:

Ragavan, V.N., Nair, P.C., Jarzebska, N., Angom, R.S., Ruta, L., Bianconi, E.,... Rodionov, R.N. (2023). A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase. Nature Communications, 14(1). https://dx.doi.org/10.1038/s41467-023-38467-9

MLA:

Ragavan, Vinitha N., et al. "A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase." Nature Communications 14.1 (2023).

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