Endothelial arginase: A new target in atherosclerosis

Yang, Zhihong; Ming, Xiu‐Fen

doi:10.1007/s11906-006-0041-8

Cited by 74 publications

(76 citation statements)

References 49 publications

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“…In contrast, nor-NOHA had no effect on ACh-induced relaxation in control rats. These findings indicate that increased arginase contributes to endothelial dysfunction, probably by limiting the L-arginine availability for NOS, as previously observed in animal models of cardiovascular diseases (19)(20)(21)(22)24). It is noteworthy that beyond its effect on vascular NO production, decreased L-arginine availability secondary to arginase up-regulation might theoretically contribute to the eNOS uncoupling recently identified in vessels of AIA rats (12).…”

Section: Discussionsupporting

confidence: 80%

“…Arginase uses L-arginine (the substrate of NOS) as substrate and can thereby limit the availability of L-arginine for NO synthesis. Consistent with this theory are the studies demonstrating that arginase inhibition enhanced NOmediated vasodilatory function under pathologic conditions such as aging, hypertension, diabetes, and atherosclerosis (19)(20)(21)(22)(23)(24). Therefore, inhibition of vascular arginase activity might represent a new pharmacologic strategy for increasing availability of arginine for NO synthesis in conditions associated with endothelial dysfunction.…”

Section: Discussionmentioning

confidence: 79%

“…Because NOS and arginase use L-arginine as a common substrate, arginase may down-regulate NO biosynthesis by competing with NOS for L-arginine degradation. Consistent with this hypothesis, increased vascular arginase activity was reported to contribute to decreased endotheliumdependent NO production in pathologic conditions such as hypertension (19,20), atherosclerosis (21), diabetes (22), and erectile dysfunction (23), or in aging (24). Moreover, even though the regulating factors of arginase expression/activity remain largely unknown, it was demonstrated that various proinflammatory cytokines can act as inducers of arginase expression in cultured endothelial cells (18,25,26).…”

mentioning

confidence: 77%

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Endothelial dysfunction in rat adjuvant‐induced arthritis: Up‐regulation of the vascular arginase pathway

Prati¹,

Berthelot²,

Wendling³

et al. 2011

Arthritis & Rheumatism

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Objective. To investigate whether arginase pathway abnormalities occur in vessels from rats with adjuvant-induced arthritis (AIA), and to determine whether the up-regulation of arginase, which reciprocally regulates nitric oxide synthase (NOS) by competing for the same substrate, L-arginine, contributes to endothelial dysfunction in AIA.Methods. We performed vascular reactivity experiments on thoracic aortic rings from AIA rats and control rats, and we investigated the response of rings to norepinephrine (NE), sodium nitroprusside (SNP), and acetylcholine (ACh). ACh-induced relaxation was evaluated in the presence (or not in the presence) of the NOS inhibitor N G -nitro-L-arginine methyl ester (L-NAME), the arginase inhibitor N -hydroxy-nor-Larginine (nor-NOHA), or both. Aortic arginase activity was measured using a spectrophotometric method, and the expression of arginase and endothelial NOS (eNOS) was evaluated by Western blotting.Results. ACh-induced vasodilation was significantly impaired in AIA rats, while the responses to NE and to SNP did not differ from those in control rats. L-NAME reduced ACh-induced vasodilation to a lesser extent in AIA rats than in control rats. Incubation of aortic rings with nor-NOHA enhanced the vascular response to ACh in AIA rats and reversed the effects of L-NAME. Compared with control rats, AIA rats exhibited increased vascular expression of arginase II (by 22%) (P < 0.05) as well as increased arginase activity (by 49%) (P < 0.05), whereas eNOS expression was unchanged. Finally, arginase activity and expression correlated positively with arthritis severity.Conclusion. Our results are consistent with the notion that arginase up-regulation plays a role in AIAassociated endothelial dysfunction. They suggest that arginase might be an attractive new target for treating endothelial dysfunction in arthritis.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 79%

mentioning

confidence: 77%

See 1 more Smart Citation

Endothelial dysfunction in rat adjuvant‐induced arthritis: Up‐regulation of the vascular arginase pathway

Prati¹,

Berthelot²,

Wendling³

et al. 2011

Arthritis & Rheumatism

View full text Add to dashboard Cite

show abstract

“…A potentially more important role that has received some attention is in the inhibition of the enzyme arginase with consequent preservation of arginine for NOS [24]. Indeed, low homoarginine concentrations have been recently shown to be associated with mortality and cardiovascular events [25].…”

Section: Discussionmentioning

confidence: 99%

Assessment of asymmetrical dimethylarginine metabolism in patients with critical illness

Ghashut

Blackwell

Ryan

et al. 2017

Eur J Clin Investigation

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Background: Critically ill patients experience metabolic disorders including hypercatabolic state and hyperglycaemia and these are associated with poor outcome. Hyperglycaemia and asymmetric dimethylarginine (ADMA) are reported to have significant influences on endothelial dysfunction. The aim of the present study was to examine the relationship between plasma asymmetric dimethylarginine (ADMA) and related arginine metabolism in patients with critical illness.

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“…Therefore, reducing the Lp-PLA2 levels and arginase activity may be an important therapeutic target in patients with renal disease. [32][33][34][35] In summary, arginase/NO pathway is impaired during the HD sessions due to several factors. Increased Lp-PLA2 mass levels contribute to impaired arginase/NO pathway via both its substrate (OxLDL) and its product (LysoPC).…”

Section: Discussionmentioning

confidence: 99%

Effects of Lipoprotein-Associated Phospholipase A2 on Arginase/Nitric Oxide Pathway in Hemodialysis Patients

et al. 2012

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Lipoprotein-associated phospholipase A2 (Lp-PLA2) and arginase are recently described inflammatory biomarkers associated with cardiovascular disease. In this study, we aimed to investigate the possible effects of serum Lp-PLA2 mass levels on arginase/nitric oxide (NO) pathway as a cardiovascular risk marker in hemodialysis (HD) patients. Fortythree HD patients and 15 healthy subjects were included in this study. Lipid profile, high sensitivity C-reactive protein (hs-CRP), albumin, creatinine, body mass index (BMI), Lp-PLA2 and total nitrite levels, and arginase activity were determined in serum samples from patients and control subjects. Lp-PLA2 levels were found to be positively correlated with arginase, triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and age and negatively correlated with high-density lipoprotein-cholesterol and total nitrite levels, while there was no correlation with BMI and hs-CRP, albumin, and creatinine levels in HD patients. We conclude that elevated Lp-PLA2 mass levels may contribute to impaired arginase/ NO pathway in HD patients and that increased the arginase activity and Lp-PLA2 mass levels with decreased total nitrite levels seem to be useful biochemical markers in terms of reflecting endothelial dysfunction and associated cardiovascular risks in HD patients.

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Endothelial arginase: A new target in atherosclerosis

Cited by 74 publications

References 49 publications

Endothelial dysfunction in rat adjuvant‐induced arthritis: Up‐regulation of the vascular arginase pathway

Endothelial dysfunction in rat adjuvant‐induced arthritis: Up‐regulation of the vascular arginase pathway

Assessment of asymmetrical dimethylarginine metabolism in patients with critical illness

Effects of Lipoprotein-Associated Phospholipase A2 on Arginase/Nitric Oxide Pathway in Hemodialysis Patients

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