Effect of Lowering Asymmetric Dimethylarginine (ADMA) on Vascular Pathology in Atherosclerotic ApoE-Deficient Mice with Reduced Renal Mass
The purpose of the work was to study the impact of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) and its degrading enzyme, dimethylarginine dimethylaminohydrolase (DDAH1), on atherosclerosis in subtotally nephrectomized (SNX) ApoE-deficient mice. Male DDAH1...
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MDPI AG
2014-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/15/4/5522 |
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| author | Johannes Jacobi Renke Maas Michaela Arend Nada Cordasic Karl F. Hilgers |
| author_facet | Johannes Jacobi Renke Maas Michaela Arend Nada Cordasic Karl F. Hilgers |
| author_sort | Johannes Jacobi |
| collection | DOAJ |
| description | The purpose of the work was to study the impact of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) and its degrading enzyme, dimethylarginine dimethylaminohydrolase (DDAH1), on atherosclerosis in subtotally nephrectomized (SNX) ApoE-deficient mice. Male DDAH1 transgenic mice (TG, n = 39) and C57Bl/6J wild-type littermates (WT, n = 27) with or without the deletion of the ApoE gene underwent SNX at the age of eight weeks. Animals were sacrificed at 12 months of age, and blood chemistry, as well as the extent of atherosclerosis within the entire aorta were analyzed. Sham treated (no renal mass reduction) ApoE-competent DDAH1 transgenic and wild-type littermates (n = 11) served as a control group. Overexpression of DDAH1 was associated with significantly lower ADMA levels in all treatment groups. Surprisingly, SNX mice did not exhibit higher ADMA levels compared to sham treated control mice. Furthermore, the degree of atherosclerosis in ApoE-deficient mice with SNX was similar in mice with or without overexpression of DDAH1. Overexpression of the ADMA degrading enzyme, DDAH1, did not ameliorate atherosclerosis in ApoE-deficient SNX mice. Furthermore, SNX in mice had no impact on ADMA levels, suggesting a minor role of this molecule in chronic kidney disease (CKD) in this mouse model. |
| first_indexed | 2024-04-12T10:03:46Z |
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| id | doaj.art-02d89f971c6d4a349ed58a1997a98108 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-12T10:03:46Z |
| publishDate | 2014-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-02d89f971c6d4a349ed58a1997a981082022-12-22T03:37:30ZengMDPI AGInternational Journal of Molecular Sciences1422-00672014-03-011545522553510.3390/ijms15045522ijms15045522Effect of Lowering Asymmetric Dimethylarginine (ADMA) on Vascular Pathology in Atherosclerotic ApoE-Deficient Mice with Reduced Renal MassJohannes Jacobi0Renke Maas1Michaela Arend2Nada Cordasic3Karl F. Hilgers4Department of Nephrology and Hypertension, Friedrich-AlexanderUniversity Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyInstitute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Nephrology and Hypertension, Friedrich-AlexanderUniversity Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Nephrology and Hypertension, Friedrich-AlexanderUniversity Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Nephrology and Hypertension, Friedrich-AlexanderUniversity Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyThe purpose of the work was to study the impact of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) and its degrading enzyme, dimethylarginine dimethylaminohydrolase (DDAH1), on atherosclerosis in subtotally nephrectomized (SNX) ApoE-deficient mice. Male DDAH1 transgenic mice (TG, n = 39) and C57Bl/6J wild-type littermates (WT, n = 27) with or without the deletion of the ApoE gene underwent SNX at the age of eight weeks. Animals were sacrificed at 12 months of age, and blood chemistry, as well as the extent of atherosclerosis within the entire aorta were analyzed. Sham treated (no renal mass reduction) ApoE-competent DDAH1 transgenic and wild-type littermates (n = 11) served as a control group. Overexpression of DDAH1 was associated with significantly lower ADMA levels in all treatment groups. Surprisingly, SNX mice did not exhibit higher ADMA levels compared to sham treated control mice. Furthermore, the degree of atherosclerosis in ApoE-deficient mice with SNX was similar in mice with or without overexpression of DDAH1. Overexpression of the ADMA degrading enzyme, DDAH1, did not ameliorate atherosclerosis in ApoE-deficient SNX mice. Furthermore, SNX in mice had no impact on ADMA levels, suggesting a minor role of this molecule in chronic kidney disease (CKD) in this mouse model.http://www.mdpi.com/1422-0067/15/4/5522ADMAsubtotal nephrectomyatherosclerosis |
| spellingShingle | Johannes Jacobi Renke Maas Michaela Arend Nada Cordasic Karl F. Hilgers Effect of Lowering Asymmetric Dimethylarginine (ADMA) on Vascular Pathology in Atherosclerotic ApoE-Deficient Mice with Reduced Renal Mass International Journal of Molecular Sciences ADMA subtotal nephrectomy atherosclerosis |
| title | Effect of Lowering Asymmetric Dimethylarginine (ADMA) on Vascular Pathology in Atherosclerotic ApoE-Deficient Mice with Reduced Renal Mass |
| title_full | Effect of Lowering Asymmetric Dimethylarginine (ADMA) on Vascular Pathology in Atherosclerotic ApoE-Deficient Mice with Reduced Renal Mass |
| title_fullStr | Effect of Lowering Asymmetric Dimethylarginine (ADMA) on Vascular Pathology in Atherosclerotic ApoE-Deficient Mice with Reduced Renal Mass |
| title_full_unstemmed | Effect of Lowering Asymmetric Dimethylarginine (ADMA) on Vascular Pathology in Atherosclerotic ApoE-Deficient Mice with Reduced Renal Mass |
| title_short | Effect of Lowering Asymmetric Dimethylarginine (ADMA) on Vascular Pathology in Atherosclerotic ApoE-Deficient Mice with Reduced Renal Mass |
| title_sort | effect of lowering asymmetric dimethylarginine adma on vascular pathology in atherosclerotic apoe deficient mice with reduced renal mass |
| topic | ADMA subtotal nephrectomy atherosclerosis |
| url | http://www.mdpi.com/1422-0067/15/4/5522 |
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