Triglyceride-glucose index levels in patients with Klinefelter syndrome and its relationship with endothelial dysfunction and insulin resistance: a cross-sectional observational study

ABSTRACT Objectives: This study aimed to investigate the triglyceride-glucose (TyG) index, which is a simple surrogate marker of insulin resistance that is associated with various cardiometabolic diseases, in patients with Klinefelter syndrome (KS). Subjects and methods: A total of 30 patients with KS (mean age: 21.53 ± 1.66 years) and 32 healthy controls (mean age: 22.07 ± 1.01 years) were included in the study.The clinical and laboratory parameters,TyG index, asymmetric dimethylarginine (ADMA) level, homeostatic model assessment of insulin resistance (HOMA-IR) score, and high-sensitivity C-reactive protein level were measured in patients with KS and healthy subjects. Results: Patients with KS had higher HOMA-IR score (p = 0.043), ADMA levels (p < 0.001), and TyG index (p = 0.031) and lower high-density lipoprotein cholesterol levels (p < 0.001) than healthy subjects. TyG index was positively correlated with plasma ADMA (r = 0.48, p < 0.001) and HOMA-IR (r = 0.36, p = 0.011). Multivariate analyses showed that total testosterone level (β = −0.44, p = 0.001) and TyG index (β = 0.29, p = 0.045) were independent determinants of plasma ADMA levels. Conclusion: Patients with KS had higher TyG indices than healthy subjects. Moreover, TyG index was independently associated with endothelial dysfunction in patients. TyG index may be a practical and useful measure to show the increased endothelial dysfunction in patients with KS.

Hepatic DDAH1 mitigates hepatic steatosis and insulin resistance in obese mice: Involvement of reduced S100A11 expression

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is an important regulator of plasma asymmetric dimethylarginine (ADMA) levels, which are associated with insulin resistance in patients with nonalcoholic fatty liver disease (NAFLD). To elucidate the role of hepatic DDAH1 in the pathogenesis of NAFLD, we used hepatocyte-specific Ddah1-knockout mice (Ddah1HKO) to examine the progress of high-fat diet (HFD)-induced NAFLD. Compared to diet-matched flox/flox littermates (Ddah1f/f), Ddah1HKO mice exhibited higher serum ADMA levels. After HFD feeding for 16 weeks, Ddah1HKO mice developed more severe liver steatosis and worse insulin resistance than Ddah1f/f mice. On the contrary, overexpression of DDAH1 attenuated the NAFLD-like phenotype in HFD-fed mice and ob/ob mice. RNA-seq analysis showed that DDAH1 affects NF-κB signaling, lipid metabolic processes, and immune system processes in fatty livers. Furthermore, DDAH1 reduces S100 calcium-binding protein A11 (S100A11) possibly via NF-κB, JNK and oxidative stress-dependent manner in fatty livers. Knockdown of hepatic S100a11 by an AAV8-shS100a11 vector alleviated hepatic steatosis and insulin resistance in HFD-fed Ddah1HKO mice. In summary, our results suggested that the liver DDAH1/S100A11 axis has a marked effect on liver lipid metabolism in obese mice. Strategies to increase liver DDAH1 activity or decrease S100A11 expression could be a valuable approach for NAFLD therapy.

Luteoloside protects the vascular endothelium against iron overload injury via the ROS/ADMA/DDAH II/eNOS/NO pathway / 中国天然药物

Iron overload injury is considered to be a part of blood stasis syndrome of arthralgia in traditional Chinese medicine. Its primary therapies include clearing heat and detoxification, activating blood circulation, and removing blood stasis. Lonicera japonica flos (LJF) has long been known as an excellent antipyretic and antidote. Luteoloside (Lut) is one of the main components of LJF and exhibits antioxidant, anti-inflammatory, and cytoprotective properties. However, the protection of Lut against iron overload injury and its underlying mechanisms remain unclear. Therefore, HUVECs were exposed to 50 μmol·L-1 iron dextran for 48 h to establish an iron overload damage model and the effects of Lut were assessed. Our results showed that 20 μmol·L-1 Lut not only increased cell viability and weakened LDH activity, but also significantly up-regulated DDAHⅡ expression and activity, increased p-eNOS/eNOS ratio and NO content, and reduced ADMA content in HUVECs exposed to iron overload. Furthermore, Lut significantly attenuated intracellular/mitochondrial ROS generation, improved SOD, CAT, and GSH-Px activities, reduced MDA content, maintained MMP, inhibited mPTP opening, prevented cyt c from mitochondria released into cytoplasm, reduced cleaved-caspase3 expression, and ultimately decreased cell apoptosis induced by iron overload. The effects of Lut were similar to those of L-arginine (an ADMA competitive substrate), cyclosporin A (a mPTP blocker agent), and edaravone (a free radical scavenger) as positive controls. However, addition of pAD/DDAH II-shRNA adenovirus reversed the above beneficial effects of Lut. In conclusion, Lut can protect HUVECs against iron overload injury via the ROS/ADMA/DDAH II/eNOS/NO pathway. The mitochondria are the target organelles of Lut's protective effects.

Plasma asymmetric dimethylarginine and its association with some of cardiovascular disease risk factors in chronic kidney disease

@#Introduction: Chronic kidney disease (CKD) usually has increase of asymmetric dimethylarginine (ADMA) levels. ADMA is a cardiovascular disease (CVD) risk factor and its elevation associated with other CVD risk factors at CKD leads to increasing risk of death. In this article, we aimed to identify levels and elevation proportion of plasma ADMA in CKD as well as association between ADMA with CVD risk factors. Methods: This cross-sectional study was performed at Hue Central Hospital from 2012-2016 on 176 CKD and 64 control subjects. ADMA levels were measured by using the enzyme linked immunosorbent assay (ELISA) method. Results: Mean ADMA level was markedly higher (p<0.001) in all patients combined (0.73±0.24µmol/L) than in control subjects (0.47±0.13µmol/L). Mean ADMA levels in advanced kidney disease were higher than control subjects. ADMA levels correlated inversely and relatively strictly to estimated glomerular filtration rate (eGFR) (r = -0.689; p<0.001), haemoglobin (r = -0.525; p<0.001) and haematocrit (r = - 0.491; p<0.001); correlated favourably and relatively strictly to serum creatinine (r = 0.569; p<0.001) and serum urea (r = 0.642; p<0.001). ADMA elevation was predicted simultaneously by eGFR<60 mL/min/1.73m2 (p<0.001), anaemia (p=0.002), body mass index (BMI) (p=0.011) and high sensitivity C-reactive protein (hs-CRP) (p=0.041). Cutoff of ≥0.68µmol/L, ADMA levels predict reduction of eGFR<60 mL/min/1.73m2 , sensitivity of 86.9 %, specificity of 82.6%, area under ROC 92.4% (95%CI: 88.6-96.1%).

Mitochondrial damage induced by iron overload viaeNOS in vascular endothelial cells / 中国药理学通报

Aim To investigate the damage of mitochondria in HUVECs cells by iron overload and the role of ADMA/eNOS/DDAHⅡ in it.Methods HUVECs cells were cultured and randomly divided into normal control (Ctrl) group, dextran iron (Iron) group and L-arginine (L-Arg) group.After 48 h, the survival rate of cells was detected by MTT assay;ADMA content and DDAHⅡactivity were measured by HPLC method;the expression of eNOS was determined by Western blot;LDH activity, MDA and NO content, and mitochondrial permeability transition pores(mPTP) openness were determined by colorimetric assay;ROS generation, mitochondrial membrane potential and apoptosis were determined by flow cytometry.Results After 48 h treatment with iron, the survival rate of HUVECs significantly decreased, while the activity of LDH in culture medium increased.The results showed that ADMA and MDA content significantly increased, NO content, DDAHⅡactivity, and the expression of eNOS markedly decreased, the generation of ROS was evidently elevated, mitochondrial membrane potential was lost apparently, mPTP openness was obvious, and the apoptosis of the HUVECs were worsened.However, as ADMA physiological antagonist, L-Arg significantly attenuated the above effects of iron.Conclusion Iron overload could damage mitochondrial function by eNOS and induce the apoptosis of HUVECs, in which ADMA/DDAHⅡ mechanism may also be engaged.

Quercetin Inhibited ADMA-induced Endoplasmic Reticulum Stress Responses and HUVECs Apotosis / 医学研究杂志

Objective To study the effect of quercetin on ADMA induced endoplasmic reticulum stress responses (ER stress).Methods Human umbilical veins endothelial cells (HUVECs) were cultured,and left untreated or challenged for 24h with 100μmol/L ADMA in the absence and presence of 20μmol/L quercetin,the PERK and IRE1 was determined by Western blot.ATF4 and CHOP mRNA was detected by RT-PCR.Cells apoptosis was detected by flow cytometry.Results ADMA induced HUVECs apoptosis.Quercetin inhibited ADMA-induced PERK and IRE1 protein expression and ATF4 and CHOP mRNA expression.At last,Quercetin inhibited ADMA-induced cells apoptosis.Conclusion ADMA induced ER stress and HUVECs apotosis while quercetin inhibited ADMA-induced ER stress and apoptosis.

Biomarcadores de função endotelial em doenças cardiovasculares: hipertensão / Biomarkers of endothelial function in cardiovascular diseases: hypertension

Resumo A incidência de hipertensão arterial sistêmica está aumentando mundialmente. Sua prevenção baseia-se na identificação dos hipertensos. Atualmente, biomarcadores são utilizados com fins de diagnosticar, estratificar e prognosticar doenças. Neste estudo, objetivou-se revisar artigos dos últimos cinco anos relacionados a biomarcadores nas doenças cardiovasculares. Pesquisaram-se dados de PubMed, SciELO, Science Direct e MEDLINE, mediante as palavras-chave: hipertensão arterial, biomarcadores cardiovasculares, óxido nítrico, função endotelial e dimetilarginina assimétrica. Os estudos levantados mostram que as doenças cardiovasculares possuem uma etiologia complexa. Neste artigo, evidenciaram-se interações entre o óxido nítrico e a dimetilarginina assimétrica na regulação, no metabolismo e na determinação dos níveis intracelulares, e reviram-se outros biomarcadores relacionados à hipertensão. Alguns estudos indicam os biomarcadores como uma ferramenta útil na predição de eventos cardíacos, e outros reportam que eles contribuem pouco para a avaliação. A seleção e combinação desses pode ser uma alternativa para validar o uso dos biomarcadores devido à pouca especificidade existente para diagnosticar a hipertensão.

Abstract The incidence of systemic arterial hypertension is increasing worldwide. The foundation of prevention is identification of people with hypertension. Nowadays, biomarkers are used to diagnose and stratify diseases and estimates prognosis. The objective of this study was to review articles published over the last 5 years on the subject of biomarkers of cardiovascular diseases. The PubMed, SciELO, Science Direct and MEDLINE databases were searched using the keywords: arterial hypertension, cardiovascular biomarkers, nitric oxide, endothelial function and asymmetric dimethylarginine. The studies reviewed show that cardiovascular diseases have complex etiologies. This article describes evidence demonstrating interactions between nitric oxide and asymmetric dimethylarginine that are involved in regulation, in metabolism, and in determination of intracellular levels, and also discusses other biomarkers related to hypertension. Some studies indicate that biomarkers are useful tools for prediction of cardiac events, whereas others state that they have little to contribute to assessments. Careful selection of tests and combinations of tests may be the key to validating use of biomarkers, in view of their low specificity for diagnosing hypertension.

Association of altered serum levels of Chemerin, Paraoxonase-1 (PON1), Asymmetric Dimethyl arginine (ADMA) and obesitin the development of Polycystic Ovarian Syndrome (PCOS) in Egyptian women

Chemerinwas recently added to the adipokine family and was identified in human ovarian follicles and follicular fluid that suggests a direct correlation between chemerin and PCOS. Asymmetric dimethyl arginine (ADMA) is involved in endothelial dysfunctionthe atherogenic potential of ADMA has been investigated in young patients with PCOS. Oxidative stress is considered to be implicated in the pathophysiology of PCOS.Paraoxonase 1 (PON1) is an antioxidant enzyme and its concentration has been shown to be inversely associated with oxidative stress. Objectives: Evaluation of serum chemerin, ADMA, PON1in obese and non-obese polycystic ovarian patients to postulate their role in pathogenesis of PCOS. Methods: Ninetynuligravida women aged 20-35 (60 with PCOS and 30 controls) were recruited. Fasting blood was obtained on day 2 or 3 of the menstrual cycle. Clinical evaluation, hormonal profile, Chemerin, ADMA and PON1 were assessed. Results: There was a significant increase in serum chemerinlevels in PCOS obese group when compared with PCOS non obese patients and healthy controls non obese and obese respectively. Serum ADMA level was increased significantly in PCOS obese group as compared to the PCOS non obese group , control non obese and control obese. Paraoxonase was decreased stepwise significantly from the control non obese group and control obese group to PCOS non obese patients then PCOS obese patients to. Conclusions: it could be suggested that increased chemerin has a role in PCOS development andaltered ADMA and PON1 associated withobesity and oxidative stress may exacerbate the condition.

Role of AGXT2 in ADMA metabolism and the development of cardiovascular and cerebrovascular diseases / 中国药理学通报

Cardiovascular and cerebrovascular diseases have be-come a great health threat.Increasing evidence has shown that both asymmetric dimethylarginine (ADMA)and symmetric dim-ethylarginine (SDMA)play important and independent roles in the development of cardiovascular and cerebrovascular diseases as well as in the prediction of cardiovascular and cerebrovascular events.Alanine-glyoxylate aminotransferase 2 (AGXT2 )is re-cently observed to be involved in ADMA metabolism.Deficiency in the expression and activity of AGXT2 may thus play a role in the development of cardiovascular and cerebrovascular diseases by affecting ADMA levels in vivo.Several single-nucleotide poly-morphisms at AGXT2 locus are observed to be associated with plasma SDMA level.This review summarizes recent advances in AGXT2 and its role in ADMA metabolism and the clinical rele-vance.

To determine the effect of endothelial dysfunction and oxidative stress markers for causing complication of the coronaryatheros clerosis / Шинэ санаа Шинэ нээлт

Coronary heart disease is a leading cause of mortality in many countries. Acute coronary syndrome is the basis pathophysiology of coronary heart disease. Complication of coronary atherosclerosis composes rupture of plaque and erosion of vulnerable plaque. Endothelial dysfunction is main influence of coronary plaque erosion. But then recently research oxidative stress and reaction ofimmunocomplex is leading cause of coronary plaque rupture. So the research background will study markers of endothelial dysfunction, oxidative stress, immune reaction in the complication of coronaryatherosclerosis. Aim: Determine the effect of some marker for causing complication of the coronary atherosclerosis.The research has been conducted using case-control study method. In the case group, patients with complication of the coronary atherosclerosis as determined by coronary angiography (stenosis >85%) as in the control group healthy people with carotid artery stenosis (<0.7mm) has been involved. In the study we defined Anti-oxLDL (anti-oxidized low density lipoprotein) using ELISA Kit (Eucardio Lab, USA) and oxLDL (oxidized low density lipoprotein) titer by ELISA Kit (Mercadio, USA), ADMA (Asymmetric dimethylarginine) titer by ELISA kit (Eucardio Lab, USA) reagents in the enzyme binding reaction. Totalantioxidant capacity (TAC) was determined by using spectrophotometer method. The average age of people involved in the research is 57.2±9.72 and for the average age is case group 28 (32%) and 50 (68%) for the control group. ADMA titer level for complication of coronaryatherosclerosis or case group is (30.1±1.98 ng/ml) which is (13.2±0.57 ng/ml) greater than the control group. It was statistically significant result (p<0.001). Also titer level for case group is oxLDL (72±2.75 mU/l), anti-oxLDL antibody (766±29.8 mU/ml), which is oxLDL (45.1±2.28 mU/l), anti-oxLDL antibody(603±17.74 mU/ml) greater than the control group. It was statistically significant result (p<0.001). But TAC titer level for control group is (116±2.47 nmol/l) which is (108.3±5.43 nmol/l) greater thanthe case group. It was not statistically significant result (p=0.098). According to the Binary LogisticRegression test the anti-oxLDL (OR=0.992, p<0.001), ADMA (OR=0.681, p<0.001), TAC (OR=1.017, p=0.105), oxLDL (OR=0.900, p<0.001) levels significantly influence the complication of coronary atherosclerosis. Therefore according to the Binary Logistic Regression test the anti-oxLDL level high significantly influence the complication of coronary atherosclerosis. Anti-oxLDL antibody titer arecorrelated directly with oxLDL (r=0.413, p<0.01), ADMA (r=0.42, p<0.001) levels. However, correlated negative directly with TAC (r=-0.233, p<0.01) level.Markers of endothelial dysfunction (ADMA OR=0.681, p<0.001) and oxidative stress (oxLDL, OR=0.900, p<0.001), (anti-oxLDL antibody, OR=0.992, p<0.001) high influence causing of complication of coronary atherosclerosis.

To determine the effect of endothelial dysfunction and oxidative stress markers for causing complication of the coronaryatheros clerosis / Шинэ санаа Шинэ нээлт

Coronary heart disease is a leading cause of mortality in many countries. Acute coronary syndrome is the basis pathophysiology of coronary heart disease. Complication of coronary atherosclerosis composes rupture of plaque and erosion of vulnerable plaque. Endothelial dysfunction is main influence of coronary plaque erosion. But then recently research oxidative stress and reaction of immunocomplex is leading cause of coronary plaque rupture. So the research background will study markers of endothelial dysfunction, oxidative stress, immune reaction in the complication of coronaryatherosclerosis. Aim: Determine the effect of some marker for causing complication of the coronary atherosclerosis. The research has been conducted using case-control study method. In the case group, patients with complication of the coronary atherosclerosis as determined by coronary angiography (stenosis >85%) as in the control group healthy people with carotid artery stenosis (<0.7mm) has been involved. In the study we defined Anti-oxLDL (anti-oxidized low density lipoprotein) using ELISA Kit (Eucardio Lab, USA) and oxLDL (oxidized low density lipoprotein) titer by ELISA Kit (Mercadio, USA), ADMA (Asymmetric dimethylarginine) titer by ELISA kit (Eucardio Lab, USA) reagents in the enzyme binding reaction. Total antioxidant capacity (TAC) was determined by using spectrophotometer method. The average age of people involved in the research is 57.2±9.72 and for the average age is case group 28 (32%) and 50 (68%) for the control group. ADMA titer level for complication of coronary atherosclerosis or case group is (30.1±1.98 ng/ml) which is (13.2±0.57 ng/ml) greater than the control group. It was statistically significant result (p<0.001). Also titer level for case group is oxLDL (72±2.75 mU/l), anti-oxLDL antibody (766±29.8 mU/ml), which is oxLDL (45.1±2.28 mU/l), anti-oxLDL antibody(603±17.74 mU/ml) greater than the control group. It was statistically significant result (p<0.001). But TAC titer level for control group is (116±2.47 nmol/l) which is (108.3±5.43 nmol/l) greater than the case group. It was not statistically significant result (p=0.098). According to the Binary Logistic Regression test the anti-oxLDL (OR=0.992, p<0.001), ADMA (OR=0.681, p<0.001), TAC (OR=1.017, p=0.105), oxLDL (OR=0.900, p<0.001) levels significantly influence the complication of coronary atherosclerosis. Therefore according to the Binary Logistic Regression test the anti-oxLDL level high significantly influence the complication of coronary atherosclerosis. Anti-oxLDL antibody titer are correlated directly with oxLDL (r=0.413, p<0.01), ADMA (r=0.42, p<0.001) levels. However, correlated negative directly with TAC (r=-0.233, p<0.01) level. Markers of endothelial dysfunction (ADMA OR=0.681, p<0.001) and oxidative stress (oxLDL, OR=0.900, p<0.001), (anti-oxLDL antibody, OR=0.992, p<0.001) high influence causing of complication of coronary atherosclerosis.

Role of ADMA-DDAH axis in the vascular endothelial dysfunction induced by uric acid / 中华肾脏病杂志

Objective To observe the formation of asymmetric dimethylarginine (ADMA)and the expression of dimethylarginine dimethylaminohydrolase 2 (DDAH-2) of human umbilical vein endothelial cells (HUVECs) stimulated by uric acid (UA), and to explore the role of ADMADDAH axis in the vascular endothelial dysfunction induced by uric acid. Methods HUVECs were cultured in M199 medium supplemented with 10% FBS. Cells were exposed to different concentrations of UA (0, 60, 120 mg/L) for 6 h and 24 h. Under different concentrations and times, the level of ADMA in cell suspension was detected by high performance liquid chromatography (HPLC) technique; the gene and protein expressions of DDAH-2 were detected by RT-PCR and Western blotting; the fluorescence intensity of intracellular 2',7'-dichlorofluorescein (DCF) which represented the productions of ROS was detected by the flow cytometry (FCM). The activity of DDAH-2 in HUVCEs which were exposed to different concentrations of UA (0, 60, 120mg/L) or UA (120 mg/L) +NAC (10 mmol/L) for 24 h was estimated by directly measuring the amount of ADMA metabolized by the enzyme and the role of NAC in the activity was studied.Results The expression of ADMA induced by urid acid was dose-depent and higher at 24 h than that at 6 h in the same dosage (all P＜0.05). The dosage and stimulation time of UA did not have any influence on the expression of intracellular DDAH-2 (all P＞0.05). When HUVECs exposed to UA (120 mg/L) for 24 h, the production of intracellular ROS was significantly increased while the activity of DDAH-2 was decreasesd (all P＜0.05) as compared to 60 mg/L stimulation. This effect could be inhibited by the intervention of anti-oxidant NAC. Conclusions The high UA stimulation on HUVECs can increase the expression of intracellular ROS and inhibit the activity of DDAH-2 which increases the concentration of ADMA by decreasing the degradation of ADMA as well as the formation of NO. DDAH-ADMA axis may participate in the vascular endothelial dysfunction induced by UA.

Asymmetric dimethylarginine and neonatal-related diseases / 国际儿科学杂志

Asymmetric dimethylarginine(ADMA) is an endogenous inhibitor of nitric oxide synthases(NOS),which is a risk marker of cardiovascular endothelial dysfunction.Recent studies found that ADMA was a predictor not only for acute cardiovascular disease,but also for critical illness and mortality.Studies have found that exogenous ADMA altered lung function and induced apoptosis in animal experiments and vitro experiments.The levels of plasma ADMA significantly increased in children with hypoxia,PPHN,brain damage,and preterm infants who required mechanical ventilation.ADMA could be a independent risk factor to predict neonatal complications and death.

Marternal Plasma ADMA Level, Placenta eNOS and Placenta Antioxidant Marker According to the Presence or Absence of Uterine Artery Notch on Color Doppler in the Third Trimester Pregnancies / 대한주산의학회잡지

PURPOSE: We examined pregnancy outcomes and maternal plasma asymmetric dimethylarginine (ADMA) concentrations in the presence or absence of uterine artery notch, and analyzed their relationships to the expression of placental endothelial nitric oxide synthase (eNOS) and antioxidant enzymes, including manganese superoxide dismutase (MnSOD), glutathione peroxidase (GPX), and catalase. METHODS: We assessed uterine artery doppler waveforms in 30 women who had been hospitalized for delivery. Plasma concentrations of ADMA were also measured. Tissue samples of placentas were obtained from 15 patients with diastolic notch and 15 patients without diastolic notch, according to uterine Doppler velocimetry analysis. We evaluated the placental expression of eNOS, MnSOD, GPX and catalase with Western blot analysis and eNOS with immunohistochemistry. RESULTS: The maternal plasma ADMA concentration increased significantly in the group with bilateral Uterine artery notch compared with the group without uterine artery notch (P=0.04). The expression of eNOS in the placenta significantly increased and the expression of MnSOD and GPX decreased significantly in the group with uterine artery notch at the third trimester. CONCLUSION: Uterine artery diastolic notch in pregnant women is associated with high maternal plasma ADMA, increased placental eNOS, and decreased MnSOD and GPX.

La dimetilarginina asimétrica, estructura e implicaciones patológicas / Asymmetric dimethylarginine, structure and pathological implications

La ateroesclerosis, es una enfermedad crónica, sistémica, inmuno-inflamatoria que afecta a la íntima arterial. La disfunción endotelial es la primera fase en la ateroesclerosis La disfunción endotelial está caracterizada por un daño y pérdida de la monocapa celular que cubre el interior de los vasos sanguíneos, denominada endotelio. Uno de los principales mediadores ara el mentenimieno de la integridad del endotelio, es el óxido nítrico (ON). La Dimetilarginina asimétrica (DMMA), es un inhibidor endógeno de la enzima sintasa del Óxido Nítrico (SON); se ha sugerido que DMAA sirve como un marcador de disfunción endotelial en enfermedades cardiovasculares. Asimismo, la DMAA representa un factor de riesgo para mortalidad cardiovascular, progresión de enfermedad crónica renal. Se ha encontrado valores elevados de DMAA en diferentes condiciones como hipercolesterolemia, aterosclerosis, hipertensión, insuficiencia renal crónica, insuficiencia crónica del corazón, diabetes y disfunsión eréctil.

Atherosclerosis is an immune inflammatory systemic, arterial disease. Endothelial dysfunction is the first stage in aterosclerosis. Atherosclerosis develops because of reactions occurring in vessel wall beginning with response to enothelial injury. Endothelial dysfunction is characterized with impairment and loss of monolayer cells covering the inside of the vessels, which is enothelium. One of the main mediators for the maintenance of the integrity of endothelium is Nitric Oxide (NO). The asymmtric Dimethilarginine (ADMA), is an endogenous inhibitor of the enzyme Nitric Oxide Synthase (NOS). ADMA has been suggested to serve as a biomarker of endothelial dysfunction in cardiovascular diseases. ADMA is a risk factor for endothelial dysfunction, cardiovascular mortality, and progression of chronic kidney disease. Elevated values of ADMA have been found in hypercholesterolemia, atherosclerosis, hypertension, chronic renal insufficiency, heart chronic failure, diabetes and erectile dysfunction.

New opinion of chronic renal disease:the effects of ADMA on the progress of the disease / 中国实用内科杂志

Asymmetric dimethylarginine(ADMA)is a natural L-arginine analogue that reduces the bioavailability of nitric oxide in plasma and various types of tissues,acting as an endogenous NO synthase inhibitor in vivo.ADMA is considered a common pathway mediating the adverse vascular effects of traditional and nontraditional risk factors.These preclinical findings are thought to be of major importance as ADMA predicts cardiovascular events and mortality in patients with chronic kidney disease(CKD).Also,ADMA uniformly predicts the progression of moderate and severe CKD.The present study summarizes the latest developments in this field.

Effect of polydatin on endothelial function in aorta vascular strips of healthy rabbits treated with ADMA / 中草药

ObjectTo study the effect of polydatin (PD) and asymmetric dimethylarginine (ADMA) on the endothelial function in aorta vascular strips of healthy rabbits and the interaction between PD and ADMA. MethodsDose-response curves of phenylephrine (PE) on the aortic strips with or without ADMA and/or PD. E max and Kd from PE were obtained and compared. ResultsNormal aortic strips could not respond to ADMA. Pretreatment with either PD or ADMA had no effect on the contractive response of aortic strips to PE. But PD could significantly weaken the contractive response of aortic strips pretreated with ADMA caused by PE in a dose-dependent manner, increase Kd and decrease E max of PE. ConclusionEither ADMA or PD alone does not influence the normal aortic strip contractive functions, the PE affinity to ?-receptor, and E max. But PD could noncompetitively antagonize the contractive reaction of aortic strips to PE in the presence of ADMA.