Nature Communications (Jun 2023)
A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase
- Vinitha N. Ragavan,
- Pramod C. Nair,
- Natalia Jarzebska,
- Ramcharan Singh Angom,
- Luana Ruta,
- Elisa Bianconi,
- Silvia Grottelli,
- Natalia D. Tararova,
- Daniel Ryazanskiy,
- Steven R. Lentz,
- Sara Tommasi,
- Jens Martens-Lobenhoffer,
- Toshiko Suzuki-Yamamoto,
- Masumi Kimoto,
- Elena Rubets,
- Sarah Chau,
- Yingjie Chen,
- Xinli Hu,
- Nadine Bernhardt,
- Peter M. Spieth,
- Norbert Weiss,
- Stefan R. Bornstein,
- Debabrata Mukhopadhyay,
- Stefanie M. Bode-Böger,
- Renke Maas,
- Ying Wang,
- Antonio Macchiarulo,
- Arduino A. Mangoni,
- Barbara Cellini,
- Roman N. Rodionov
Affiliations
- Vinitha N. Ragavan
- Department of Internal Medicine III, Technische Universität Dresden
- Pramod C. Nair
- Department of Clinical Pharmacology, College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Bedford Park
- Natalia Jarzebska
- Department of Internal Medicine III, Technische Universität Dresden
- Ramcharan Singh Angom
- Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science
- Luana Ruta
- Department of Pharmaceutical Sciences, University of Perugia
- Elisa Bianconi
- Department of Pharmaceutical Sciences, University of Perugia
- Silvia Grottelli
- Department of Medicine and Surgery, University of Perugia
- Natalia D. Tararova
- DAPCEL, Inc.
- Daniel Ryazanskiy
- DAPCEL, Inc.
- Steven R. Lentz
- Department of Internal Medicine, The University of Iowa Carver College of Medicine
- Sara Tommasi
- Department of Clinical Pharmacology, College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Bedford Park
- Jens Martens-Lobenhoffer
- Institute of Clinical Pharmacology, Otto von Guericke University
- Toshiko Suzuki-Yamamoto
- Department of Nutritional Science, Faculty of Health and Welfare Science, Okayama Prefectural University
- Masumi Kimoto
- Department of Nutritional Science, Faculty of Health and Welfare Science, Okayama Prefectural University
- Elena Rubets
- Department of Internal Medicine III, Technische Universität Dresden
- Sarah Chau
- Department of Cardiovascular Medicine, Mayo Clinic College of Medicine and Science
- Yingjie Chen
- Department of Physiology and Biophysics, University of Mississippi Medical Center
- Xinli Hu
- Institute of Molecular Medicine, Beijing University
- Nadine Bernhardt
- Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden
- Peter M. Spieth
- Department of Anesthesiology and Critical Care Medicine, University Hospital Dresden, Technische Universität Dresden
- Norbert Weiss
- Department of Internal Medicine III, Technische Universität Dresden
- Stefan R. Bornstein
- Department of Internal Medicine III, Technische Universität Dresden
- Debabrata Mukhopadhyay
- Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science
- Stefanie M. Bode-Böger
- Institute of Clinical Pharmacology, Otto von Guericke University
- Renke Maas
- Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg
- Ying Wang
- Department of Cardiovascular Medicine, Mayo Clinic College of Medicine and Science
- Antonio Macchiarulo
- Department of Pharmaceutical Sciences, University of Perugia
- Arduino A. Mangoni
- Department of Clinical Pharmacology, College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Bedford Park
- Barbara Cellini
- Department of Medicine and Surgery, University of Perugia
- Roman N. Rodionov
- Department of Internal Medicine III, Technische Universität Dresden
- DOI
- https://doi.org/10.1038/s41467-023-38467-9
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 16
Abstract
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.
