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) |
|---|---|
| Pages (from-to) | H159-H166 |
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 302 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2012 |
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Keywords
- Fibrosis
- Oxidative stress
- Vascular stiffness
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
Cite this
Diabetes-induced vascular dysfunction involves arginase. / Romero, Maritza J.; Iddings, Jennifer A.; Platt, Daniel H.; Irfan Ali, M.; Cederbaum, Stephen D.; Stepp, David W.; Caldwell, Ruth B.; Caldwell, Robert W.
In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 302, No. 1, 01.01.2012, p. H159-H166.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Diabetes-induced vascular dysfunction involves arginase
AU - Romero, Maritza J.
AU - Iddings, Jennifer A.
AU - Platt, Daniel H.
AU - Irfan Ali, M.
AU - Cederbaum, Stephen D.
AU - Stepp, David W.
AU - Caldwell, Ruth B.
AU - Caldwell, Robert W.
PY - 2012/1/1
Y1 - 2012/1/1
N2 - 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.
AB - 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.
KW - Fibrosis
KW - Oxidative stress
KW - Vascular stiffness
UR - http://www.scopus.com/inward/record.url?scp=84255192664&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84255192664&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00774.2011
DO - 10.1152/ajpheart.00774.2011
M3 - Article
C2 - 22058149
AN - SCOPUS:84255192664
VL - 302
SP - H159-H166
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 1
ER -