RGD Reference Report - Diabetes-induced coronary vascular dysfunction involves increased arginase activity. - Rat Genome Database

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Diabetes-induced coronary vascular dysfunction involves increased arginase activity.

Authors: Romero, MJ  Platt, DH  Tawfik, HE  Labazi, M  El-Remessy, AB  Bartoli, M  Caldwell, RB  Caldwell, RW 
Citation: Romero MJ, etal., Circ Res. 2008 Jan 4;102(1):95-102. Epub 2007 Oct 25.
RGD ID: 4142848
Pubmed: PMID:17967788   (View Abstract at PubMed)
PMCID: PMC2822539   (View Article at PubMed Central)
DOI: DOI:10.1161/CIRCRESAHA.107.155028   (Journal Full-text)

Increases in arginase activity have been reported in a variety of disease conditions characterized by vascular dysfunction. Arginase competes with NO synthase for their common substrate arginine, suggesting a cause and effect relationship. We tested this concept by experiments with streptozotocin diabetic rats and high glucose (HG)-treated bovine coronary endothelial cells (BCECs). Our studies showed that diabetes-induced impairment of vasorelaxation to acetylcholine was correlated with increases in reactive oxygen species and arginase activity and arginase I expression in aorta and liver. Treatment of diabetic rats with simvastatin (5 mg/kg per day, subcutaneously) or L-citrulline (50 mg/kg per day, orally) blunted these effects. Acute treatment of diabetic coronary arteries with arginase inhibitors also reversed the impaired vasodilation to acetylcholine. Treatment of BCECs with HG (25 mmol/L, 24 hours) also increased arginase activity. This effect was blocked by treatment with simvastatin (0.1 micromol/L), the Rho kinase inhibitor Y-27632 (10 micromol/L), or L-citrulline (1 mmol/L). Superoxide and active RhoA levels also were elevated in HG-treated BCECs. Furthermore, HG significantly diminished NO production in BCECs. Transfection of BCECs with arginase I small interfering RNA prevented the rise in arginase activity in HG-treated cells and normalized NO production, suggesting a role for arginase I in reduced NO production with HG. These results indicate that increased arginase activity in diabetes contributes to vascular endothelial dysfunction by decreasing L-arginine availability to NO synthase.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  ISOArg1 (Rattus norvegicus)4142848; 4142848protein:increased expression:aorta and liver (rat)RGD 
Experimental Diabetes Mellitus  IEP 4142848protein:increased expression:aorta and liver (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Arg1  (arginase 1)

Genes (Mus musculus)
Arg1  (arginase, liver)

Genes (Homo sapiens)
ARG1  (arginase 1)


Additional Information