| Diabetes-induced vascular dysfunction involves arginase I. | |
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MedLine Citation:
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PMID: 22058149 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Arginase can cause vascular dysfunction by competing with nitric oxide synthase for l-arginine and by increasing cell proliferation and collagen formation, which promote vascular fibrosis/stiffening. We have shown that increased arginase expression/activity contribute to vascular endothelial cell (EC) dysfunction. Here, we examined the roles of the two arginase isoforms, arginase I and II (AI and AII, respectively), in this process. Experiments were performed using streptozotocin-induced diabetic mice: wild-type (WT) mice and knockout mice lacking the AII isoform alone (AI(+/+)AII(-/-)) or in combination with partial deletion of AI (AI(+/-)AII (-/-)). EC-dependent vasorelaxation of aortic rings and arterial fibrosis and stiffness were assessed in relation to arginase activity and expression. Diabetes reduced mean EC-dependent vasorelaxation markedly in diabetic WT and AI(+/+)AII(-/-) aortas (53% and 44% vs. controls, respectively) compared with a 27% decrease in AI(+/-)AII (-/-) vessels. Coronary fibrosis was also increased in diabetic WT and AI(+/+)AII(-/-) mice (1.9- and 1.7-fold vs. controls, respectively) but was not altered in AI(+/-)AII (-/-) diabetic mice. Carotid stiffness was increased by 142% in WT diabetic mice compared with 51% in AI(+/+)AII(-/-) mice and 19% in AI(+/-)AII (-/-) mice. In diabetic WT and AI(+/+)AII(-/-) mice, aortic arginase activity and AI expression were significantly increased compared with control mice, but neither parameter was altered in AI(+/-)AII (-/-) mice. In summary, AI(+/-)AII (-/-) mice exhibit better EC-dependent vasodilation and less vascular stiffness and coronary fibrosis compared with diabetic WT and AI(+/+)AII(-/-) mice. These data indicate a major involvement of AI in diabetes-induced vascular dysfunction. |
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Authors:
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Maritza J Romero; Jennifer A Iddings; Daniel H Platt; M Irfan Ali; Stephen D Cederbaum; David W Stepp; Ruth B Caldwell; Robert W Caldwell |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-11-04 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 302 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2011-12-27 Completed Date: 2012-02-14 Revised Date: 2012-05-23 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H159-66 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Toxicology, Georgia Health Sciences University, Augusta, 30912, USA. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aorta / enzymology, physiopathology Arginase / genetics, metabolism* Arteries / drug effects, enzymology*, pathology, physiopathology Carotid Arteries / enzymology, physiopathology Compliance Coronary Vessels / enzymology, physiopathology Diabetes Mellitus, Experimental / complications*, enzymology, genetics, pathology, physiopathology Diabetic Angiopathies / enzymology, etiology*, genetics, pathology, physiopathology Dose-Response Relationship, Drug Fibrosis Hydrogen Peroxide / metabolism Hydroxyproline / metabolism Lipid Peroxidation / drug effects Mice Mice, Inbred C57BL Mice, Knockout Superoxides / metabolism Vasoconstriction Vasoconstrictor Agents / pharmacology Vasodilation* Vasodilator Agents / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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R01-EY-11766/EY/NEI NIH HHS; R01-HL-70215/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Vasoconstrictor Agents; 0/Vasodilator Agents; 11062-77-4/Superoxides; 51-35-4/Hydroxyproline; 7722-84-1/Hydrogen Peroxide; EC 3.5.3.1/Arg1 protein, mouse; EC 3.5.3.1/Arg2 protein, mouse; EC 3.5.3.1/Arginase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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