Dimethylarginine Dimethylaminohydrolase Promotes Endothelial Repair After Vascular Injury
| Autor: | John P. Cooke, Karsten Sydow, Hakuoh Konishi |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Neointima
Male medicine.medical_specialty Endothelium Neovascularization Physiologic Vasodilation Mice Transgenic 030204 cardiovascular system & hematology Arginine Nitric Oxide Sensitivity and Specificity Amidohydrolases 03 medical and health sciences chemistry.chemical_compound Mice Random Allocation 0302 clinical medicine Species Specificity Internal medicine medicine Animals Humans Vascular Diseases 030304 developmental biology Cell Proliferation Probability 0303 health sciences Matrigel biology business.industry Immunohistochemistry Dimethylargininase Surgery Nitric oxide synthase Endothelial stem cell Femoral Artery Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Endocrinology chemistry Enzyme Induction biology.protein Endothelium Vascular Cardiology and Cardiovascular Medicine business Asymmetric dimethylarginine |
| Zdroj: | Journal of the American College of Cardiology. (10):1099-1105 |
| ISSN: | 0735-1097 |
| DOI: | 10.1016/j.jacc.2006.10.068 |
| Popis: | ObjectivesWe sought to determine if a reduction in asymmetric dimethylarginine (ADMA) enhances endothelial regeneration.BackgroundAsymmetric dimethylarginine is an endogenous inhibitor of nitric oxide synthase (NOS). Increased plasma levels of ADMA are associated with endothelial vasodilator dysfunction in patients with vascular disease or risk factors. Asymmetric dimethylarginine is eliminated largely by the action of dimethylarginine dimethylaminohydrolase (DDAH), which exists in 2 isoforms. Dimethylarginine dimethylaminohydrolase-1 transgenic (TG) mice manifest increased DDAH activity, reduced plasma and tissue ADMA levels, increased nitric oxide synthesis, and reduced systemic vascular resistance.MethodsThe left femoral arteries of DDAH1 TG mice and wild-type (WT) mice were injured by a straight spring wire, and regeneration of the endothelial cell (EC) monolayer was assessed. Endothelial sprouting was assayed with growth factor-reduced Matrigel.ResultsRegeneration of the EC monolayer was more complete 1 week after injury in TG mice (WT vs. TG: 40.0 ± 6.5% vs. 61.2 ± 6.4%, p < 0.05). The number of CD45 positive cells at the injured sites was reduced by 62% in DDAH TG mice (p < 0.05). Four weeks after injury, the neointima area and intima/media ratio were attenuated in DDAH TG mice (WT vs. TG: 0.049 ± 0.050 mm2vs. 0.031 ± 0.060 mm2, 3.1 ± 0.5 vs. 1.7 ± 0.2, respectively, p < 0.05). Endothelial cell sprouting from vascular segments increased in TG mice (WT vs. TG: 24.3 ± 3.9 vs. 39.0 ± 2.2, p < 0.05).ConclusionsWe find for the first time an important role for DDAH in EC regeneration and in neointima formation. Strategies to enhance DDAH expression or activity might be useful in restoring the endothelial monolayer and in treating vascular disease. |
| Databáze: | OpenAIRE |
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