Associations of Biopterins and ADMA with Vascular Function in Peripheral Microcirculation from Patients with Chronic Kidney Disease
We hypothesized that patients with chronic kidney disease (CKD) display an altered plasma amino acid (AA) metabolomic profile that could contribute to abnormal vascular maintenance of peripheral circulation in uremia. The relationships between plasma AAs and endothelial and vascular smooth muscle fu...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5582 |
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| author | Samsul Arefin Lars Löfgren Peter Stenvinkel Anna B. Granqvist Karolina Kublickiene |
| author_facet | Samsul Arefin Lars Löfgren Peter Stenvinkel Anna B. Granqvist Karolina Kublickiene |
| author_sort | Samsul Arefin |
| collection | DOAJ |
| description | We hypothesized that patients with chronic kidney disease (CKD) display an altered plasma amino acid (AA) metabolomic profile that could contribute to abnormal vascular maintenance of peripheral circulation in uremia. The relationships between plasma AAs and endothelial and vascular smooth muscle function in the microcirculation of CKD patients are not well understood. The objective of this study is to investigate to what extent the levels of AAs and its metabolites are changed in CKD patients and to test their relationship with endothelial and vascular smooth muscle function. Patients with CKD stages 3 and 5 and non-CKD controls are included in this study. We report that there was a significant reduction of the biopterin (BH<sub>4</sub>/BH<sub>2</sub>) ratio, which was accompanied by increased plasma levels of BH<sub>2</sub>, asymmetric dimethylarginine (ADMA) and citrulline in patients with CKD-5 vs. CKD-3 vs. controls. In vivo augmentation index measurement showed a positive association with ADMA in all participants. The contribution of nitric oxide, assessed by ex vivo assay, showed a negative association with creatinine, ADMA and citrulline in all participants. In CKD-5, BH<sub>4</sub> negatively correlated with ADMA and ornithine levels, and the ex vivo endothelium-mediated dilatation positively correlated with phenylalanine levels. In conclusion, uremia is associated with alterations in AA metabolism that may affect endothelium-dependent dilatation and vascular stiffness in microcirculation. Interventional strategies aiming to normalize the AA metabolism could be of interest as treatment options. |
| first_indexed | 2024-03-11T06:26:04Z |
| format | Article |
| id | doaj.art-6555e08fe6e3448ab7b2eda680d9a2eb |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:26:04Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6555e08fe6e3448ab7b2eda680d9a2eb2023-11-17T11:36:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246558210.3390/ijms24065582Associations of Biopterins and ADMA with Vascular Function in Peripheral Microcirculation from Patients with Chronic Kidney DiseaseSamsul Arefin0Lars Löfgren1Peter Stenvinkel2Anna B. Granqvist3Karolina Kublickiene4Department of Clinical Science, Intervention & Technology, Division of Renal Medicine, Karolinska Institutet, 141 86 Stockholm, SwedenEarly CVRM, BioPharmaceuticals R&D, AstraZeneca, 431 50 Mölndal, SwedenDepartment of Clinical Science, Intervention & Technology, Division of Renal Medicine, Karolinska Institutet, 141 86 Stockholm, SwedenEarly CVRM, BioPharmaceuticals R&D, AstraZeneca, 431 50 Mölndal, SwedenDepartment of Clinical Science, Intervention & Technology, Division of Renal Medicine, Karolinska Institutet, 141 86 Stockholm, SwedenWe hypothesized that patients with chronic kidney disease (CKD) display an altered plasma amino acid (AA) metabolomic profile that could contribute to abnormal vascular maintenance of peripheral circulation in uremia. The relationships between plasma AAs and endothelial and vascular smooth muscle function in the microcirculation of CKD patients are not well understood. The objective of this study is to investigate to what extent the levels of AAs and its metabolites are changed in CKD patients and to test their relationship with endothelial and vascular smooth muscle function. Patients with CKD stages 3 and 5 and non-CKD controls are included in this study. We report that there was a significant reduction of the biopterin (BH<sub>4</sub>/BH<sub>2</sub>) ratio, which was accompanied by increased plasma levels of BH<sub>2</sub>, asymmetric dimethylarginine (ADMA) and citrulline in patients with CKD-5 vs. CKD-3 vs. controls. In vivo augmentation index measurement showed a positive association with ADMA in all participants. The contribution of nitric oxide, assessed by ex vivo assay, showed a negative association with creatinine, ADMA and citrulline in all participants. In CKD-5, BH<sub>4</sub> negatively correlated with ADMA and ornithine levels, and the ex vivo endothelium-mediated dilatation positively correlated with phenylalanine levels. In conclusion, uremia is associated with alterations in AA metabolism that may affect endothelium-dependent dilatation and vascular stiffness in microcirculation. Interventional strategies aiming to normalize the AA metabolism could be of interest as treatment options.https://www.mdpi.com/1422-0067/24/6/5582chronic kidney diseasebiopterinsasymmetric dimethylarginineamino acidsvascular function |
| spellingShingle | Samsul Arefin Lars Löfgren Peter Stenvinkel Anna B. Granqvist Karolina Kublickiene Associations of Biopterins and ADMA with Vascular Function in Peripheral Microcirculation from Patients with Chronic Kidney Disease International Journal of Molecular Sciences chronic kidney disease biopterins asymmetric dimethylarginine amino acids vascular function |
| title | Associations of Biopterins and ADMA with Vascular Function in Peripheral Microcirculation from Patients with Chronic Kidney Disease |
| title_full | Associations of Biopterins and ADMA with Vascular Function in Peripheral Microcirculation from Patients with Chronic Kidney Disease |
| title_fullStr | Associations of Biopterins and ADMA with Vascular Function in Peripheral Microcirculation from Patients with Chronic Kidney Disease |
| title_full_unstemmed | Associations of Biopterins and ADMA with Vascular Function in Peripheral Microcirculation from Patients with Chronic Kidney Disease |
| title_short | Associations of Biopterins and ADMA with Vascular Function in Peripheral Microcirculation from Patients with Chronic Kidney Disease |
| title_sort | associations of biopterins and adma with vascular function in peripheral microcirculation from patients with chronic kidney disease |
| topic | chronic kidney disease biopterins asymmetric dimethylarginine amino acids vascular function |
| url | https://www.mdpi.com/1422-0067/24/6/5582 |
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