Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oestrogen replacement therapy (ERT) has been shown to lead to favourable changes in the cardiovascular risk profile of postmenopausal women. Part of this effect is ascribed to increased production or bioavailability of nitric oxide (NO). We have tested the hypothesis that ERT lowers plasma levels of asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of NO synthase (NOS). In a randomized double-blind study design, 40 hysterectomized postmenopausal women received conjugated equine oestrogen (CEE; 0.625 mg/day; n =14), the selective oestrogen receptor modulator raloxifene (150 mg/day; n =13) or placebo ( n =13). At baseline and after 6, 12 and 24 months of treatment, plasma was analysed for levels of arginine, ADMA, and symmetrical dimethylarginine (SDMA), a stereoisomer of ADMA that does not inhibit NOS. An overall treatment effect on ADMA levels was observed in the CEE group ( P =0.004 compared with placebo), but not in the raloxifene group ( P =0.50). The decrease of ADMA levels by CEE treatment was consistent over the 2-year study period, without significant differences between the effects at 6, 12 and 24 months. The average post-baseline change in ADMA in the CEE group compared with placebo was -7.8% (95% confidence interval -12.8% to -2.9%; P =0.003). Arginine or SDMA levels did not change during treatment in any of the groups. Thus ERT with oral conjugated oestrogen, but not with raloxifene, significantly reduced plasma concentrations of the cardiovascular risk factor ADMA in healthy postmenopausal women.
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PMID:Oestrogen replacement therapy lowers plasma levels of asymmetrical dimethylarginine in healthy postmenopausal women. 1268 48

In 1992, asymmetrical dimethylarginine (ADMA) was first described as an endogenous inhibitor of the arginine-nitric oxide (NO) pathway. From then, its role in regulating NO production has attracted increasing attention. Nowadays, ADMA is regarded as a novel cardiovascular risk factor. The role of the kidney and the liver in the metabolism of ADMA has been extensively studied and both organs have proven to play a key role in the elimination of ADMA. Although the liver removes ADMA exclusively via degradation by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), the kidney uses both metabolic degradation via DDAH and urinary excretion to eliminate ADMA. Modulating activity and/or expression of DDAH is still under research and may be a potential therapeutic approach to influence ADMA plasma levels. Interestingly, next to its association with cardiovascular disease, ADMA also seems to play a role in other clinical conditions, such as critical illness, hepatic failure, and preeclampsia. To elucidate the clinical significance of ADMA in these conditions, the field of research must be enlarged.
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PMID:The clinical significance of asymmetric dimethylarginine. 1684 5

Telmisartan, in addition to blocking angiotensin (Ang) II type 1 receptor (AT(1)R), activates peroxisome proliferator activated receptor gamma (PPARgamma) signaling that interferes with nitric oxide (NO) system. Because aging of endothelial cells (ECs) is hallmarked by a reduction in NO synthesis, we hypothesized that telmisartan increases NO formation by regulated asymmetrical dimethylarginine (ADMA)-dimethylarginine dimethylaminohydrolase (DDAH)-system through blocking AT(1)R and activating PPARgamma signaling. To test this hypothesis, ECs were cultured with telmisartan, eprosartan, Ang II, and GW9662 (PPARgamma antagonist) until the twelfth passage. During the process of aging, PPARgamma protein expression decreased significantly, whereas the expression of AT(1)R increased. Telmisartan reversed these effects and dose-dependently decreased reactive oxygen species and 8-iso-prostaglandin (PG) F(2alpha) formation. This effect was associated with an upregulated activity and protein expression of DDAH, accompanied by a decrease in ADMA concentration, an increase in NO metabolites, and delayed senescence. Blockade of PPARgamma signaling by GW9662 or PPARgamma small-interference RNA prevented the effect of telmisartan on ADMA-DDAH-NO system. Coincubation with Ang II did not affect the effect of telmisartan-delayed senescence, whereas Ang II itself accelerated endothelial aging. Moreover, AT(1)R blocker eprosartan that did not influence PPARgamma protein expression had no effect on ADMA system and senescence. We have demonstrated that telmisartan mainly by activating PPARgamma signaling can alter the catabolism and release of ADMA as an important cardiovascular risk factor. We therefore propose that telmisartan translationally and posttranslationally upregulated DDAH expression via activation of PPARgamma signaling, causing ADMA to diminish and increase NO synthesis sufficient to delay senescence.
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PMID:Effect of telmisartan on nitric oxide--asymmetrical dimethylarginine system: role of angiotensin II type 1 receptor gamma and peroxisome proliferator activated receptor gamma signaling during endothelial aging. 1825 Mar 62