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

doi:10.1038/s41467-023-38467-9

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. SpiethNorbert Weiss, Stefan R. Bornstein, Debabrata Mukhopadhyay, Stefanie M. Bode-Böger, Renke Maas, Ying Wang, Antonio Macchiarulo, Arduino A. Mangoni, Barbara Cellini, Roman N. Rodionov

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	3392
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-38467-9
State	Published - Dec 2023

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Ragavan, V. N., Nair, P. C., Jarzebska, N., Angom, R. S., Ruta, L., Bianconi, E., Grottelli, S., Tararova, N. D., Ryazanskiy, D., Lentz, S. R., Tommasi, S., Martens-Lobenhoffer, J., Suzuki-Yamamoto, T., Kimoto, M., Rubets, E., Chau, S., Chen, Y., Hu, X., Bernhardt, N., ... Rodionov, R. N. (2023). A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase. Nature communications, 14(1), Article 3392. https://doi.org/10.1038/s41467-023-38467-9

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, 'A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase', Nature communications, vol. 14, no. 1, 3392. https://doi.org/10.1038/s41467-023-38467-9

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title = "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 still unclear if DDAH2 may be a potential target for ADMA-lowering therapies or if drug development efforts should focus on DDAH2{\textquoteright}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.",

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AU - Ragavan, Vinitha N.

AU - Nair, Pramod C.

AU - Jarzebska, Natalia

AU - Angom, Ramcharan Singh

AU - Ruta, Luana

AU - Bianconi, Elisa

AU - Grottelli, Silvia

AU - Tararova, Natalia D.

AU - Ryazanskiy, Daniel

AU - Lentz, Steven R.

AU - Tommasi, Sara

AU - Martens-Lobenhoffer, Jens

AU - Suzuki-Yamamoto, Toshiko

AU - Kimoto, Masumi

AU - Rubets, Elena

AU - Chau, Sarah

AU - Chen, Yingjie

AU - Hu, Xinli

AU - Bernhardt, Nadine

AU - Spieth, Peter M.

AU - Weiss, Norbert

AU - Bornstein, Stefan R.

AU - Mukhopadhyay, Debabrata

AU - Bode-Böger, Stefanie M.

AU - Maas, Renke

AU - Wang, Ying

AU - Macchiarulo, Antonio

AU - Mangoni, Arduino A.

AU - Cellini, Barbara

AU - Rodionov, Roman N.

PY - 2023/12

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N2 - 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.

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

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