Abstract
Arginase can cause vascular dysfunction by competing with nitric oxide synthase for L-argi-nine 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.
Original language | English (US) |
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Pages (from-to) | H159-H166 |
Journal | American Journal of Physiology - Heart and Circulatory Physiology |
Volume | 302 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2012 |
Keywords
- Fibrosis
- Oxidative stress
- Vascular stiffness
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)