A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-38467-9 |
| _version_ | 1797806600443920384 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Vinitha N. Ragavan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T06:09:43Z |
| format | Article |
| id | doaj.art-c46891e5d10241cf95a530af2ca4d6b5 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-13T06:09:43Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-c46891e5d10241cf95a530af2ca4d6b52023-06-11T11:19:53ZengNature PortfolioNature Communications2041-17232023-06-0114111610.1038/s41467-023-38467-9A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolaseVinitha N. Ragavan0Pramod C. Nair1Natalia Jarzebska2Ramcharan Singh Angom3Luana Ruta4Elisa Bianconi5Silvia Grottelli6Natalia D. Tararova7Daniel Ryazanskiy8Steven R. Lentz9Sara Tommasi10Jens Martens-Lobenhoffer11Toshiko Suzuki-Yamamoto12Masumi Kimoto13Elena Rubets14Sarah Chau15Yingjie Chen16Xinli Hu17Nadine Bernhardt18Peter M. Spieth19Norbert Weiss20Stefan R. Bornstein21Debabrata Mukhopadhyay22Stefanie M. Bode-Böger23Renke Maas24Ying Wang25Antonio Macchiarulo26Arduino A. Mangoni27Barbara Cellini28Roman N. Rodionov29Department of Internal Medicine III, Technische Universität DresdenDepartment of Clinical Pharmacology, College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Bedford ParkDepartment of Internal Medicine III, Technische Universität DresdenDepartment of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and ScienceDepartment of Pharmaceutical Sciences, University of PerugiaDepartment of Pharmaceutical Sciences, University of PerugiaDepartment of Medicine and Surgery, University of PerugiaDAPCEL, Inc.DAPCEL, Inc.Department of Internal Medicine, The University of Iowa Carver College of MedicineDepartment of Clinical Pharmacology, College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Bedford ParkInstitute of Clinical Pharmacology, Otto von Guericke UniversityDepartment of Nutritional Science, Faculty of Health and Welfare Science, Okayama Prefectural UniversityDepartment of Nutritional Science, Faculty of Health and Welfare Science, Okayama Prefectural UniversityDepartment of Internal Medicine III, Technische Universität DresdenDepartment of Cardiovascular Medicine, Mayo Clinic College of Medicine and ScienceDepartment of Physiology and Biophysics, University of Mississippi Medical CenterInstitute of Molecular Medicine, Beijing UniversityDepartment of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität DresdenDepartment of Anesthesiology and Critical Care Medicine, University Hospital Dresden, Technische Universität DresdenDepartment of Internal Medicine III, Technische Universität DresdenDepartment of Internal Medicine III, Technische Universität DresdenDepartment of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and ScienceInstitute of Clinical Pharmacology, Otto von Guericke UniversityInstitute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-NürnbergDepartment of Cardiovascular Medicine, Mayo Clinic College of Medicine and ScienceDepartment of Pharmaceutical Sciences, University of PerugiaDepartment of Clinical Pharmacology, College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Bedford ParkDepartment of Medicine and Surgery, University of PerugiaDepartment of Internal Medicine III, Technische Universität DresdenAbstract 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.https://doi.org/10.1038/s41467-023-38467-9 |
| spellingShingle | 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 A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase Nature Communications |
| title | A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase |
| title_full | A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase |
| title_fullStr | A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase |
| title_full_unstemmed | A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase |
| title_short | A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase |
| title_sort | multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase |
| url | https://doi.org/10.1038/s41467-023-38467-9 |
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multicentricconsortiumstudydemonstratesthatdimethylargininedimethylaminohydrolase2isnotadimethylargininedimethylaminohydrolase AT debabratamukhopadhyay multicentricconsortiumstudydemonstratesthatdimethylargininedimethylaminohydrolase2isnotadimethylargininedimethylaminohydrolase AT stefaniembodeboger multicentricconsortiumstudydemonstratesthatdimethylargininedimethylaminohydrolase2isnotadimethylargininedimethylaminohydrolase AT renkemaas multicentricconsortiumstudydemonstratesthatdimethylargininedimethylaminohydrolase2isnotadimethylargininedimethylaminohydrolase AT yingwang multicentricconsortiumstudydemonstratesthatdimethylargininedimethylaminohydrolase2isnotadimethylargininedimethylaminohydrolase AT antoniomacchiarulo multicentricconsortiumstudydemonstratesthatdimethylargininedimethylaminohydrolase2isnotadimethylargininedimethylaminohydrolase AT arduinoamangoni multicentricconsortiumstudydemonstratesthatdimethylargininedimethylaminohydrolase2isnotadimethylargininedimethylaminohydrolase AT barbaracellini multicentricconsortiumstudydemonstratesthatdimethylargininedimethylaminohydrolase2isnotadimethylargininedimethylaminohydrolase AT romannrodionov multicentricconsortiumstudydemonstratesthatdimethylargininedimethylaminohydrolase2isnotadimethylargininedimethylaminohydrolase |