YI 1.4 Increases in Circulating Trimethylamine-N-Oxide Contribute to the Development of Age-Related Aortic Stiffness in Humans and Mice
Age-related increases in aortic stiffness, assessed by pulse wave velocity (PWV), predict cardiovascular (CV)-related mortality, but the upstream drivers are incompletely understood. Purpose: To determine if higher circulating levels of the gut microbiome-derived metabolite trimethylamine-N-oxide (...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-12-01
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| Series: | Artery Research |
| Subjects: | |
| Online Access: | https://www.atlantis-press.com/article/125950031/view |
| _version_ | 1818150242210545664 |
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| author | Abigail G Casso Rachel A Gioscia-Ryan Zachary J Sapinsley Nicholas S VanDongen Amy E Bazzoni Andrew P Neilson Melanie C Zigler Kevin P Davy Douglas R Seals Vienna E Brunt |
| author_facet | Abigail G Casso Rachel A Gioscia-Ryan Zachary J Sapinsley Nicholas S VanDongen Amy E Bazzoni Andrew P Neilson Melanie C Zigler Kevin P Davy Douglas R Seals Vienna E Brunt |
| author_sort | Abigail G Casso |
| collection | DOAJ |
| description | Age-related increases in aortic stiffness, assessed by pulse wave velocity (PWV), predict cardiovascular (CV)-related mortality, but the upstream drivers are incompletely understood.
Purpose: To determine if higher circulating levels of the gut microbiome-derived metabolite trimethylamine-N-oxide (TMAO) contribute to age-related aortic stiffening.
Methods and Results: Plasma TMAO concentrations were higher in healthy middle-aged-to-older (45–79 y; N = 83) vs. young (18–27 y; N = 14) humans (6.3 ± 0.6 vs. 1.8 ± 0.3 μM; p < 0.01) and positively related to carotid-femoral (c-f) PWV (r2 = 0.15, p < 0.0001). To determine the role of TMAO in established age-related aortic stiffness, we supplemented old mice (27 mo; N = 12–16/group) with 1% 3,3-dimethyl-1-butanol (DMB; suppresses microbiota-dependent TMAO production) in drinking water for 8–10 weeks vs. normal drinking water (control). Relative to young mice (3 mo; N = 23), old mice had higher aortic (a) PWV (412 ± 17 vs. 349 ± 11 cm/s; p < 0.01), but DMB had no effect on aPWV (p = 0.58 vs. control) despite suppressing plasma TMAO (control: 8.7 ± 6.3 vs. DMB: 4.3 ± 1.2 µM, p = 0.07) to young levels (3.8 ± 2.6 µM). Next, to determine if TMAO contributes to the development of aortic stiffening, we initiated DMB at mid-life (18 mo; i.e., before the onset of stiffening; N = 8–21/age/treatment). aPWV was similar between young and 18 month-old mice (363 ± 5 cm/s; p = 0.58), but increased progressively with age in control mice (24 mo: 401 ± 13 cm/s, p = 0.03 vs. young; 27 mo: 442 ± 10 cm/s, p < 0.001 vs. young), whereas age-related increases in PWV were considerably attenuated by DMB (24 mo: 359 ± 9 cm/s; 27 mo: 388 ± 10 cm/s, both p < 0.01 vs. control).
Conclusions: Age-related increases in TMAO contribute to the development of aortic stiffness. TMAO-targeted interventions initiated in mid-life may prevent/delay age-related aortic stiffening and reduce CV risk.
Funding: HL134887-02S1, AG060884, HL140875, AG000279. |
| first_indexed | 2024-12-11T13:19:49Z |
| format | Article |
| id | doaj.art-3a8b1dee1b01463e9bc2d518fbf70fdf |
| institution | Directory Open Access Journal |
| issn | 1876-4401 |
| language | English |
| last_indexed | 2024-12-11T13:19:49Z |
| publishDate | 2020-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Artery Research |
| spelling | doaj.art-3a8b1dee1b01463e9bc2d518fbf70fdf2022-12-22T01:05:54ZengBMCArtery Research1876-44012020-12-0126Supplement 110.2991/artres.k.201209.004YI 1.4 Increases in Circulating Trimethylamine-N-Oxide Contribute to the Development of Age-Related Aortic Stiffness in Humans and MiceAbigail G CassoRachel A Gioscia-RyanZachary J SapinsleyNicholas S VanDongenAmy E BazzoniAndrew P NeilsonMelanie C ZiglerKevin P DavyDouglas R SealsVienna E BruntAge-related increases in aortic stiffness, assessed by pulse wave velocity (PWV), predict cardiovascular (CV)-related mortality, but the upstream drivers are incompletely understood. Purpose: To determine if higher circulating levels of the gut microbiome-derived metabolite trimethylamine-N-oxide (TMAO) contribute to age-related aortic stiffening. Methods and Results: Plasma TMAO concentrations were higher in healthy middle-aged-to-older (45–79 y; N = 83) vs. young (18–27 y; N = 14) humans (6.3 ± 0.6 vs. 1.8 ± 0.3 μM; p < 0.01) and positively related to carotid-femoral (c-f) PWV (r2 = 0.15, p < 0.0001). To determine the role of TMAO in established age-related aortic stiffness, we supplemented old mice (27 mo; N = 12–16/group) with 1% 3,3-dimethyl-1-butanol (DMB; suppresses microbiota-dependent TMAO production) in drinking water for 8–10 weeks vs. normal drinking water (control). Relative to young mice (3 mo; N = 23), old mice had higher aortic (a) PWV (412 ± 17 vs. 349 ± 11 cm/s; p < 0.01), but DMB had no effect on aPWV (p = 0.58 vs. control) despite suppressing plasma TMAO (control: 8.7 ± 6.3 vs. DMB: 4.3 ± 1.2 µM, p = 0.07) to young levels (3.8 ± 2.6 µM). Next, to determine if TMAO contributes to the development of aortic stiffening, we initiated DMB at mid-life (18 mo; i.e., before the onset of stiffening; N = 8–21/age/treatment). aPWV was similar between young and 18 month-old mice (363 ± 5 cm/s; p = 0.58), but increased progressively with age in control mice (24 mo: 401 ± 13 cm/s, p = 0.03 vs. young; 27 mo: 442 ± 10 cm/s, p < 0.001 vs. young), whereas age-related increases in PWV were considerably attenuated by DMB (24 mo: 359 ± 9 cm/s; 27 mo: 388 ± 10 cm/s, both p < 0.01 vs. control). Conclusions: Age-related increases in TMAO contribute to the development of aortic stiffness. TMAO-targeted interventions initiated in mid-life may prevent/delay age-related aortic stiffening and reduce CV risk. Funding: HL134887-02S1, AG060884, HL140875, AG000279.https://www.atlantis-press.com/article/125950031/viewAgingstiffnessmetabolitestranslational |
| spellingShingle | Abigail G Casso Rachel A Gioscia-Ryan Zachary J Sapinsley Nicholas S VanDongen Amy E Bazzoni Andrew P Neilson Melanie C Zigler Kevin P Davy Douglas R Seals Vienna E Brunt YI 1.4 Increases in Circulating Trimethylamine-N-Oxide Contribute to the Development of Age-Related Aortic Stiffness in Humans and Mice Artery Research Aging stiffness metabolites translational |
| title | YI 1.4 Increases in Circulating Trimethylamine-N-Oxide Contribute to the Development of Age-Related Aortic Stiffness in Humans and Mice |
| title_full | YI 1.4 Increases in Circulating Trimethylamine-N-Oxide Contribute to the Development of Age-Related Aortic Stiffness in Humans and Mice |
| title_fullStr | YI 1.4 Increases in Circulating Trimethylamine-N-Oxide Contribute to the Development of Age-Related Aortic Stiffness in Humans and Mice |
| title_full_unstemmed | YI 1.4 Increases in Circulating Trimethylamine-N-Oxide Contribute to the Development of Age-Related Aortic Stiffness in Humans and Mice |
| title_short | YI 1.4 Increases in Circulating Trimethylamine-N-Oxide Contribute to the Development of Age-Related Aortic Stiffness in Humans and Mice |
| title_sort | yi 1 4 increases in circulating trimethylamine n oxide contribute to the development of age related aortic stiffness in humans and mice |
| topic | Aging stiffness metabolites translational |
| url | https://www.atlantis-press.com/article/125950031/view |
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