dimethylarginine and Coronary-Artery-Disease

 Exposure to tobacco smoke is associated with a higher cardiovascular risk, especially in patients with coronary artery disease (CAD). .  The aim of the study was to evaluate the effect of active and passive tobacco smoking on the activity of endothelial markers in advanced atherosclerosis..  We studied 181 consecutive patients with advanced CAD (53 women and 128 men) aged 60 ±8 years, including 102 active self‑declared smokers (56.3%). We determined plasma asymmetric dimethylarginine (ADMA), thrombomodulin (TM), and plasminogen activator inhibitor‑1 (PAI‑1) levels, along with serum cotinine concentrations as a marker of tobacco smoking. .  Plasma ADMA levels were higher in active smokers compared with nonsmokers (0.60 ±0.09 μmol/l vs. 0.49 ±0.08 μmol/l, P <0.001). There were similar intergroup differences in TM (4.60 ±2.11 ng/ml vs. 3.0 ±1.7 ng/ml, P <0.0001) and PAI‑1 levels (30.3 ±12.4 ng/ml vs. 23.6 ±11.3 ng/ml, P <0.0001). We observed positive correlations between cotinine and ADMA (r = 0.71, P <0.0001), TM (r = 0.53, P <0.0001), and PAI‑1 (r = 0.58, P <0.0001). In 21 patients (26.6%) who declared to be nonsmokers, cotinine levels (mean, 6.30 ±22.5 ng/ml) significantly correlated with ADMA, TM, and PAI‑1 (all P <0.001). A multivariate regression analysis showed that cotinine was an independent predictor of ADMA, TM, and PAI‑1 in the whole patient group. .  Despite long‑lasting endothelial injury in advanced CAD, continued cigarette smoking is able to further enhance endothelial damage by increasing ADMA levels and resultant inhibition of fibrinolysis.

Topics: Arginine; Biomarkers; Comorbidity; Coronary Artery Disease; Cotinine; Disease Progression; Endothelium, Vascular; Female; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Plasminogen Activator Inhibitor 1; Regression Analysis; Smoking; Thrombomodulin; Tobacco Smoke Pollution

Extracts from pine tree bark containing a variety of flavonoids have been used in traditional medicine. Pycnogenol is a proprietary bark extract of the French maritime pine tree (Pinus pinaster ssp. atlantica) that exerts antioxidative, anti-inflammatory, and anti-platelet effects. However, the effects of Pycnogenol on endothelial dysfunction, a precursor of atherosclerosis and cardiovascular events, remain still elusive.. Twenty-three patients with coronary artery disease (CAD) completed this randomized, double-blind, placebo-controlled cross-over study. Patients received Pycnogenol (200 mg/day) for 8 weeks followed by placebo or vice versa on top of standard cardiovascular therapy. Between the two treatment periods, a 2-week washout period was scheduled. At baseline and after each treatment period, endothelial function, non-invasively assessed by flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound, biomarkers of oxidative stress and inflammation, platelet adhesion, and 24 h blood pressure monitoring were evaluated. In CAD patients, Pycnogenol treatment was associated with an improvement of FMD from 5.3 ± 2.6 to 7.0 ± 3.1 (P < 0.0001), while no change was observed with placebo (5.4 ± 2.4 to 4.7 ± 2.0; P = 0.051). This difference between study groups was significant [estimated treatment effect 2.75; 95% confidence interval (CI): 1.75, 3.75, P < 0.0001]. 15-F(2t)-Isoprostane, an index of oxidative stress, significantly decreased from 0.71 ± 0.09 to 0.66 ± 0.13 after Pycnogenol treatment, while no change was observed in the placebo group (mean difference 0.06 pg/mL with an associated 95% CI (0.01, 0.11), P = 0.012]. Inflammation markers, platelet adhesion, and blood pressure did not change after treatment with Pycnogenol or placebo.. This study provides the first evidence that the antioxidant Pycnogenol improves endothelial function in patients with CAD by reducing oxidative stress.

Topics: Adult; Aged; Anti-Inflammatory Agents; Antihypertensive Agents; Antioxidants; Arginine; Biomarkers; Blood Platelets; Blood Pressure; C-Reactive Protein; Coronary Artery Disease; Cross-Over Studies; Double-Blind Method; Endothelin-1; Endothelium, Vascular; Female; Flavonoids; Humans; Male; Middle Aged; Oxidative Stress; Plant Extracts; Prospective Studies; Shear Strength; Treatment Outcome; Vasodilation; Vasodilator Agents

We explored the role of asymmetrical dimethylarginine (ADMA) as a cause of endothelial dysfunction induced by systemic inflammation. In vitro data suggest that ADMA bioavailability is regulated by proinflammatory stimuli, but it is unclear whether ADMA is a link between inflammation and endothelial dysfunction in humans. In study 1 we recruited 351 patients with coronary artery disease (CAD) and 87 healthy controls. In study 2 we recruited 69 CAD, 69 healthy, and 10 patients with rheumatoid arthritis, whereas in study 3, 22 healthy and 70 CAD subjects were randomly assigned to Salmonella typhii vaccination (n=11 healthy and n=60 CAD) or placebo (n=11 healthy and n=10 CAD). Circulating interleukin 6/ADMA and flow-mediated dilation (FMD) were measured at 0 and 8 hours. In study 1, ADMA was inversely correlated with FMD in healthy individuals and CAD patients (P<0.0001 for both). However, interleukin 6 was inversely correlated with FMD (P<0.0001) in healthy subjects but not in CAD patients. The positive correlation between ADMA and interleukin 6 was stronger in healthy (r=0.515; P<0.0001) compared with CAD (r=0.289; P=0.0001) subjects. In study 2, both patients with rheumatoid arthritis and CAD had higher interleukin 6 (P<0.0001) and ADMA (P=0.004) but lower FMD (P=0.001) versus healthy subjects. In study 3, vaccination increased interleukin 6 in healthy (P<0.001) and CAD (P<0.001) subjects. FMD was reduced in healthy subjects (P<0.05), but its reduction in CAD was borderline. Vaccination increased ADMA only in healthy subjects (P<0.001). Systemic, low-grade inflammation leads to increased ADMA that may induce endothelial dysfunction. This study demonstrated that ADMA may be a link between inflammation and endothelial dysfunction in humans.

Topics: Arginine; Atherosclerosis; Coronary Artery Disease; Disease Progression; Endothelium, Vascular; Female; Follow-Up Studies; Humans; Inflammation; Male; Pilot Projects; Prognosis; Vasodilation

Accumulating evidence has stipulated a strong correlation between vitamin D (vitD) deficiency and cardiovascular disease (CVD); however, a mechanistic link is missing. This study investigated the association of vitD with endothelial dysfunction parameters. Subjects comprised male patients with verified coronary artery disease (CAD) (n=69) and age- and sex-matched controls (n=20). 25-Hydroxyvitamin D [25(OH)D] was determined using high performance liquid chromatography with ultraviolet detection whereas asymmetric and symmetric dimethylarginine (ADMA and SDMA, respectively) were determined by liquid chromatography-mass spectrometry. Nitric oxide (NO) was determined spectrophotometrically and high-sensitivity C-reactive protein (hs-CRP) was determined using enzyme-linked immunosorbent assay (ELISA). Comparison of mean 25(OH)D concentrations of patients and controls yielded a significant result (p=0.0002). 25(OH)D2 was dominant in patients whereas 25(OH)D3 was dominant in controls (p=0.003 and 0.001, respectively). Comparison of mean ADMA and SDMA concentrations of patients exhibiting normal and suboptimal vitD yielded insignificant results (p=0.692 and 0.998, respectively). Significant results were obtained from the comparison of mean hs-CRP and NO concentrations of patients exhibiting normal and suboptimal vitD (p=0.035 and 0.031, respectively). Results suggest involvement of vitD with the NO system, however not via modulation of the dimethylated arginines. A potential anti-inflammatory activity for vitD is also raised.

Topics: 25-Hydroxyvitamin D 2; Adult; Arginine; C-Reactive Protein; Case-Control Studies; Coronary Artery Disease; Endothelium, Vascular; Humans; Male; Middle Aged; Nitric Oxide; Vitamin D; Vitamin D Deficiency

The aim of this study was to examine the contribution of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS) and a novel marker of vascular endothelial dysfunction, and thrombin-activatable fibrinolysis inhibitor (TAFI), a risk factor for venous thrombosis, to the predisposition of coronary restenosis following stent implantation in coronary artery disease (CAD) patients. Thirty-seven patients with CAD were recruited from the Kobry El Obba Military Hospital, Cairo, Egypt. The patients were hospitalized for coronary angiography and coronary stenting (CS). Overnight fasting blood samples were collected from patients prior to CS and four months later for the determination of plasma ADMA and TAFI levels. The patients underwent follow-up coronary angiography to reveal in-stent restenosis. The results showed that plasma ADMA levels in CAD patients were significantly higher than those reported for healthy subjects. ADMA levels were significantly increased by 30% in CAD patients four months following CS. CAD patients who developed in-stent restenosis had a 35% increase in ADMA levels following CS. TAFI levels were not significantly changed after CS in CAD patients or in any of the subgroups. In conclusion, ADMA, but not TAFI, is linked to the predisposition of in-stent restenosis following CS.

Topics: Arginine; Carboxypeptidase B2; Coronary Angiography; Coronary Artery Disease; Humans; Middle Aged; Smoking; Stents

Coronary artery disease is the most common cause of death in Turkey and the world. Asymmetric dimethylarginine is the major inhibitor of nitric oxide synthesis in humans. It has been shown that increased levels of asymmetric dimethylarginine is associated with endothelial dysfunction and increased atherogenesis. In this study, we aimed to investigate whether asymmetric dimethylarginine level is related with conventional risk score systems in subjects who had family history of coronary artery disease.. Fifty two subjects within 20-40 years old of whom first degree relatives had myocardial infarction at young ages and 26 age and sex matched control subjects were included in this cross-sectional observational study. Frequency of diabetes, hyperlipidemia, smoking and serum levels of homocysteine, high-sensitive C-reactive protein (hsCRP) and asymmetric dimethylarginine were compared between risk group and control subjects. Relation of asymmetric dimethylarginine level with Framingham and TEKHARF risk scores was also compared. Chi-square and Mann-Whitney U tests were used to compare categorical and continuous variables, respectively.. Fasting serum glucose, triglyceride, high-density lipoprotein, diastolic blood pressure, waist circumference and TEKHARF scores were increased in the subjects who had family history of myocardial infarction. Total cholesterol, low-density lipoprotein, hsCRP, homocysteine, creatinine and Framingham risk score were similar in studied groups . Asymmetric dimethylarginine levels were 0.1 µmol/L higher in the risk group; however this difference could not reach significance (0.7±0.1 µmol/l vs 0.8±0.1 µmol/l; p=0.061).. Measurement of serum asymmetric dimethylarginine levels did not reveal utility in defining conventional coronary artery disease risk score systems in cases that had positive family history. Larger studies including patients with different risk tertiles are needed.

Topics: Adult; Arginine; Case-Control Studies; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Male; Risk Assessment; Risk Factors; Young Adult

Topics: Arginine; Biomarkers; C-Reactive Protein; Coronary Artery Disease; Humans; Lipoproteins, LDL; Troponin

Serum asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), L-arginine, and C-reactive protein (hsCRP) levels were assessed in 100 Egyptian male 35-50-year-old patients with coronary artery disease (CAD), classified into: patients under conservative medical treatment, patients directed for percutaneous coronary interventions, patients directed for coronary artery bypass graft operation and patients suffering from acute myocardial infarction. Age- and sex-matched controls (n=100) were included. Correlation between serum levels of biomarkers and dimethylarginine dimethylaminohydrolase-2 (DDAH-2) genotypes was studied. No association between biomarkers and carriage of the specific DDAH2 SNP2 (-449C/G, rs805305) genotype was detected. Further studies are required to confirm the contribution of the biomarkers in the predisposition of CAD.

Topics: Adult; Amidohydrolases; Arginine; Coronary Artery Bypass; Coronary Artery Disease; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide

We hypothesized that an integrated assessment of arginine with its catabolic products might better predict cardiovascular risks than arginine levels alone.. Arginine is the sole nitrogen source for nitric oxide (NO) synthesis. The major catabolic products of arginine are ornithine and citrulline.. Plasma levels of free arginine, ornithine, citrulline, and the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) were measured with liquid chromatography coupled with tandem mass spectrometry. We examined the relationship of global arginine bioavailability ratio (GABR) (defined as arginine/[ornithine + citrulline]) versus arginine and its catabolic metabolites to prevalence of significantly obstructive coronary artery disease (CAD) and incidence of major adverse cardiovascular events (MACE) (death, myocardial infarction, stroke) over a 3-year follow-up in 1,010 subjects undergoing elective cardiac catheterization.. Patients with significantly obstructive CAD had significantly lower GABR (median [interquartile range]: 1.06 [0.75 to 1.31] vs. 1.27 [0.96 to 1.73], p < 0.001) and arginine levels [mean: 68 +/- 20 micromol/l vs. 74 +/- 24 micromol/l, p < 0.001) than those without significantly obstructive CAD. After adjusting for Framingham risk score, C-reactive protein, and renal function, lower GABR (but not arginine levels) and higher citrulline levels remained significantly associated with both the prevalence of significantly obstructive CAD (adjusted odds ratio: 3.93, p < 0.001, and 5.98, p < 0.001, respectively) and 3-year risk for the incidence of MACE (adjusted hazard ratio: 1.98, p = 0.025, and 2.40, p = 0.01, respectively) and remained significant after adjusting for ADMA.. GABR might serve as a more comprehensive concept of reduced NO synthetic capacity compared with systemic arginine levels. Diminished GABR and high citrulline levels are associated with both development of significantly obstructive atherosclerotic CAD and heightened long-term risk for MACE.

Topics: Aged; Arginine; Biological Availability; C-Reactive Protein; Citrulline; Confidence Intervals; Coronary Artery Disease; Female; Humans; Male; Middle Aged; Nitric Oxide Synthase; Odds Ratio; Ornithine; Prognosis; Prospective Studies; Risk Assessment; Risk Factors

The increase of circulating asymmetric dimethylarginine (ADMA) concentrations, a competitive inhibitor of the nitric oxide synthases, is associated with an increased cardiovascular risk and is considered to play a role in endothelial dysfunction. Recently, ADMA production was observed in stimulated human peripheral mononuclear cells. In this study, we examined a potential relationship between concentrations of ADMA and of the immune activation marker neopterin in patients scheduled for coronary angiography. In a cross-sectional approach, blood concentrations of ADMA, homocysteine, neopterin, folic acid and vitamins B6 and B12 were compared in 2030 patients, which were recruited as participants of the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study. ADMA concentrations did not differ between patients with coronary artery disease (CAD) (mean +/- SD: 0.82 +/- 0.15 micromol/l) and controls (0.81 +/- 0.14 micromol/l; Welch's t-test: P = n.s.). ADMA concentrations correlated with homocysteine (r(s) = 0.207) and vitamin B6 (r(s) = -0.190), and an even stronger correlation with neopterin (r(s) = 0.276; all P < 0.0001) was observed. In conclusion, increased ADMA concentrations in patients at risk for atherosclerosis are associated with increased neopterin concentrations. Data suggest that immune activation may contribute to increased ADMA production in CAD patients.

Topics: Arginine; Chromatography, High Pressure Liquid; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Folic Acid; Homocysteine; Humans; Middle Aged; Neopterin; Risk Factors; Vitamin B 12; Vitamin B 6

Atherosclerosis is a chronic inflammatory disease, which selectively involves the arteries in the vascular system. Atherosclerosis develops because of reactions occurring in vessel wall beginning with response to endothelial injury. Endothelial dysfunction is characterized with impairment and loss of monolayer cells covering the inside of the vessels, which is endothelium. Endothelial dysfunction is the first stage in atherosclerosis. Coronary angiogenesis and collateral growth are chronic adaptations to myocardial ischemia to restore coronary blood flow and salvage myocardium in the ischemic region. Nitric oxide (NO) which represents the status of endothelial health plays a major role in collateral vessel development. Asymmetric dimethylarginine (ADMA) which is endogenous inhibitor of NO synthesis may impair the effective coronary collateral vessel development. Increased plasma ADMA levels are related with poor coronary collateral development. ADMA may be responsible for the difference in coronary collateral vessel development among similar patients with coronary artery disease. Nitric oxide inhibitors have a determinative relation with endothelial cell functions which may be integral prerequisite in all steps of collateral development. The aim of this review is to evaluate the interrelations between ADMA and collateral growth.

Topics: Arginine; Atherosclerosis; Cardiovascular Diseases; Collateral Circulation; Coronary Artery Disease; Humans; Male; Nitric Oxide; Nitric Oxide Synthase Type III; Risk Factors

As an endogenous inhibitor of nitric oxide production, asymmetric dimethylarginine (ADMA) is reported to be associated with coronary artery disease (CAD).. We measured plasma levels of ADMA, nitrate + nitrite (NOx), total homocysteine (tHCY), and renal function in 106 people with angiographic evidence of coronary artery disease (CAD), including 46 with single vessel disease and 60 with double/triple vessel disease, and in 70 age-matched individuals without any angiography evidence of CAD. Also the levels of these parameters were evaluated according to their history of MI. Plasma tHcy and ADMA were measured by HPLC and the levels of NOx using the Griess reaction.. Levels of ADMA, ACE and tHcy levels were significantly higher and NO level was significantly lower in CAD patients compared with controls but there were no significant differences among patients with or without history of MI and between patients with single compared to those with double/triple vessel disease. Additionally a negative correlation was found between ADMA-NOx (r = -0.396, p = 0.001) and between tHcy-NOx (r = -0.262, p = 0.027). In the entire study group, ADMA level was significantly higher in patients with creatinine clearance (CrCl) < 91 mL/min than in patients with CrCl > or = 91 mL/min (0.60 +/- 0.23 micromoles/L versus 0.49 +/- 0.25 micromoles/L, p = 0.05).. We suggest that there is an abnormal plasma ADMA-to-NO balance in patients with documented CAD and that this may be due at least in part to an associated reduction in renal function.

Topics: Aged; Arginine; Case-Control Studies; Coronary Artery Disease; Female; Homeostasis; Homocysteine; Humans; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Nitric Oxide

Functional changes of the vessel wall--specifically dysfunction of endothelial cells--may precede the formation of frank plaques at the initiation of atherosclerosis. Clinically endothelial function and dysfunction can be measured by angiography or ultrasound techniques. Another possibility is the measurement of circulating markers of endothelial dysfunction in human plasma, such as the endogenous NOS inhibitor ADMA (asymmetric dimethylarginine). In our recent studies we were able to show that ADMA accumulates in the presence of metabolic changes such as hyperhomocysteinemia, insulin resistance and type-2 diabetes, and that these elevations of plasma ADMA correlate well with the amount of endothelial dysfunction and with NO bioavailability. Furthermore ADMA was shown to be dynamically regulated and to play an important patho-physiologic role in myocardial ischemia and reperfusion. Thus, measurements of plasma ADMA in patients could help to screen for manifestations of atherosclerosis. Moreover attempts to reduce plasma and tissue ADMA could potentially play an important role in the treatment of endothelial dysfunction, atherosclerosis, but also of ischemia reperfusion injury.

Topics: Arginine; Coronary Artery Disease; Diabetes Mellitus, Type 2; Endothelium, Vascular; Homocysteine; Humans; Insulin Resistance; Myocardial Reperfusion Injury; Nitric Oxide; Nitric Oxide Synthase; Statistics as Topic

To investigate whether the plasma asymmetrical dimethylarginine (ADMA) level correlates with the extent and severity of coronary atherosclerosis.. 110 consecutive patients undergoing coronary angiography were divided into five groups according to the result thereof: control group (n = 22, with normal coronary artery), mild coronary artery disease (CAD) group (n = 21, with stenosis < 50% of the major coronary arteries), single branch CAD group III (n = 22, with stenosis >/= 50% of one major coronary artery); double branch CAD group IV (n = 23, with stenosis >/= 50% of two major coronary arteries); and multi-branch CAD group (n = 22, with significant stenosis >/= 50% of more than two major coronary arteries or companies with stenosis of left major coronary). ELISA was used to detect the plasma ADMA. Nitric acid reductase method and colorimetry were used to measure the levels of plasma nitric oxide (NO) and nitrogen oxide synthase (NOS). The relationship between the plasma ADMA and severity of CAD was analyzed.. The plasma ADMA levels of in last three a groups were 1.52 micromol/L +/- 0.61 micromol/L, 1.67 micromol/L +/- 0.80 micromol/L, and 2.60 micromol/L +/- 0.62 micromol/L all significantly higher than that of the control group (0.79 micromol/L +/- 0.54 micromol/L, P < 0.01). The plasma NO and NOS levels of the multi-branch CAD group were significantly lower than those of the other groups (all P < 0.01), and there were not significant differences in Plasma NO and NOS levels among the other groups. Multivariate stepwise logistic regression analysis showed that the plasma ADMA level was significantly positively correlated with the severity of coronary atherosclerosis (r = 0.684, P = 0.007) and total cholesterol and triglyceride (r = 0.623 and 0.536 respectively), and significantly negatively correlated with the NO and NOS levels (r = -0.709 and -0.701 respectively).. Correlated significantly with the severity of coronary atherosclerosis, the plasma ADMA level may become a novel marker of CAD.

Topics: Aged; Arginine; Coronary Angiography; Coronary Artery Disease; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Nitric Oxide; Nitric Oxide Synthase

Coronary endothelial dysfunction (CED) precedes atherosclerosis and is associated with cardiovascular events. Both CED and erectile dysfunction (ED) are partly mediated by impairment in the nitric oxide pathway. ED is associated with established coronary atherosclerosis, but its relationship with early coronary atherosclerosis and CED is unknown. This study was designed to test the hypothesis that CED is associated with ED in men with early coronary atherosclerosis. Moreover, the role of the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) was investigated; ADMA is a novel endogenous competitive inhibitor of nitric oxide synthase and has been shown to be an independent marker for cardiovascular disease.. Fifty-six men without obstructive coronary artery disease (CAD) who underwent coronary endothelial function testing were studied. ADMA levels were determined and all men were asked to complete the International Index of Erectile Function-5 questionnaire to assess erectile function. Patients were divided according to the presence (n = 32) or absence (n = 24) of CED. Men with CED had significant impairment of erectile function (P = 0.008) and significantly higher ADMA levels (0.50 +/- 0.06 vs. 0.45 +/- 0.07 ng/mL, P = 0.017) compared with men with normal endothelial function. Erectile function positively correlated with coronary endothelial function. This correlation was independent of age, body mass index, high-density lipoprotein, C-reactive protein, homeostasis model assessment of insulin resistance index, and smoking status.. CED is independently associated with ED and plasma ADMA concentration in men with early coronary atherosclerosis. This study further supports the role of the endothelium in systemic vascular diseases and the role of ADMA in the systemic manifestations of endothelial dysfunction.

Topics: Arginine; C-Reactive Protein; Coronary Artery Disease; Endothelium, Vascular; Erectile Dysfunction; Humans; Male; Middle Aged; Risk Factors

Symmetrical dimethylarginine (SDMA) is the structural isomer of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine. Whereas the major route of asymmetric dimethylarginine elimination is the hydrolytic degradation by dimethylarginine dimethylaminohydrolase, SDMA is eliminated by renal excretion. SDMA does not directly inhibit NOS but is a competitor of arginine transport. This study showed for the first time that measurement of SDMA can be a marker of estimated GFR and extent of coronary artery disease (CAD). In 97 patients with CAD, SDMA was a marker of estimated GFR. On multiple regression analysis of the CAD parameter stenosis score, SDMA was the only parameter retained. In addition, endothelial cells from the third passage were cultured in medium that contained 70 micromol/L arginine and was incubated for 24 h in the presence of various concentration of SDMA (0, 2, 5, 10, and 100 micromol/L). The levels of nitrate and nitrite in conditioned media, the protein expression of NOS, and the content of reactive oxygen species in endothelial cells were determined. SDMA inhibited dose dependently the NO synthesis in intact endothelial cells, whereas it had no effect on protein expression of NOS. This effect was associated with an increase in reactive oxygen species. Co-incubation with L-arginine but not D-arginine reversed the effect of SDMA on NOS pathway. Our data suggest that SDMA reduced the endothelial NO synthesis, probably by limiting L-arginine supply to NOS. It is concluded that SDMA might be a useful parameter for detecting patients in very early stages of chronic kidney disease and for determining their risk for developing cardiovascular disease.

Topics: Aged; Arginine; Biomarkers; Case-Control Studies; Cells, Cultured; Coronary Artery Disease; Endothelial Cells; Enzyme Inhibitors; Humans; Isomerism; Kidney Failure, Chronic; Kidney Function Tests; Middle Aged; Nitric Oxide; Nitric Oxide Synthase Type III; Risk Factors

We investigated the role of asymmetric dimethylarginine (ADMA) for clinical outcome of patients with unstable angina.. Forty-five patients with stable angina, 36 patients with unstable angina, and 40 healthy controls were included in this study. Coronary artery disease (CAD) patients were prospectively followed for 1 year. ADMA levels were measured at baseline and after 6 weeks using a validated ELISA. Baseline ADMA concentration in controls was significantly lower than in patients with CAD (0.59+/-0.23 vs. 0.76+/-0.17 micromol/L; P<0.001). Patients with unstable angina had significantly higher baseline ADMA levels than patients with stable angina (0.82+/-0.18 vs. 0.73+/-0.15 micromol/L; P=0.01). There was a significant reduction of ADMA levels at 6 weeks after percutaneous coronary intervention (PCI) in patients with unstable angina who experienced no recurrent cardiovascular event (from 0.81+/-0.14 to 0.73+/-0.19 micromol/L; P<0.05). In contrast, patients with unstable angina who had an event showed no significant decrease in ADMA at 6 weeks. Actuarial survival analysis showed a significantly higher event rate in patients with persistently elevated ADMA plasma concentrations.. ADMA is significantly elevated in patients with unstable angina. A reduced ADMA level at 6 weeks after PCI may indicate a decreased risk of recurrent cardiovascular events.

Topics: Adult; Aged; Aged, 80 and over; Angina Pectoris; Angina, Unstable; Arginine; Case-Control Studies; Coronary Artery Disease; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Recurrence; Risk Factors

Coronary artery disease (CAD) and erectile dysfunction (ED) of vascular origin are closely related and share common risk factors. The endogenous NO synthase inhibitor asymmetrical dimethylarginine (ADMA) has recently been identified as an independent risk marker for cardiovascular disease and it was the purpose of the present study to investigate the role ADMA in ED with and without underlying CAD.. We determined plasma ADMA levels in 132 men with ED. Patients were divided into a group of 56 men with underlying CAD (ED-CAD) and a group of 76 men without clinical evidence for underlying CAD (ED-No-CAD). Diagnosis of ED was based on the International Index of Erectile Function Score (IIEF-5). Plasma ADMA concentrations in the ED-CAD group were elevated as compared to the ED-No-CAD group, median (IQR): 0.76 (0.65-0.91) micromol/l ADMA vs. 0.49 (0.36-0.71) micromol/l, p < 0.001. In a multiple logistic regression analysis adjusting for hypertension, hypercholesterolemia, low HDL cholesterol and diabetes or fasting glucose > or =6.1 mmol/l, ADMA remained a strong and independent predictor for presence of CAD. Odds ratios for second and third tertiles as compared to lowest tertile of plasma ADMA were 3.3 (95%CI, 1.1-10.3; p = 0.041) and 8.7 (95%CI, 2.8-27.2; p < 0.001), respectively.. As elevation of ADMA has been found to be associated with many risk factors for both CAD and ED, our data provide further strong evidence for the close interrelation of CAD and ED. Determination of ADMA may help to identify underlying cardiovascular disease in men with ED.

Topics: Age Distribution; Aged; Arginine; Biomarkers; Case-Control Studies; Comorbidity; Confidence Intervals; Coronary Artery Disease; Erectile Dysfunction; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Prevalence; Prognosis; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index