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Biomedical subjects

Charalambos Antoniades

Publications and source records attributed to Charalambos Antoniades.

At least 19 recordsLinked to original sources
PubMed2006

Evidence that non-lipid cardiovascular risk factors are associated with high prevalence of coronary artery disease in patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia.

BACKGROUND: Heterozygous familial hypercholesterolemia (hFH) and familial combined hyperlipidemia (FCH) have been associated with increased risk for coronary artery disease (CAD), but the impact of traditional risk factors to the incidence of CAD in these patients remains unknown. The present study evaluates the contribution of such risk factors to the development of CAD in these two dyslipidemic populations. METHODS: This cross-sectional study enrolled a total 1306 subjects; 600 individuals with hFH (mean age 41+/-13 years, 261 males and 339 females), and 706 individuals with FCH (mean age 49+/-11 years, 463 males and 243 females). Blood samples were collected after 12 hours fasting period, and serum lipids were determined. Multivariate logistic regression models were used to estimate the odds ratios of CAD based on the type of hyperlipidemia, after adjustment for demographic characteristics and risk factors. RESULTS: Subjects with FCH were older (P<0.001), and they had a significantly increased prevalence of hypertension, diabetes and metabolic syndrome (40 vs. 10%, 13 vs. 2% and 41 vs. 6% respectively, all P<0.001) compared to the hFH group. Total cholesterol, LDL-cholesterol, and apolipoprotein B levels were higher (all P<0.001) in hFH subjects. Although in multivariate analysis lipid abnormalities found in hFH were associated with increased risk of CAD (P<0.001) compared with lipid abnormalities of FCH, the overall prevalence of CAD was similar between the two groups (16.7 vs. 15.3%, P=NS). CONCLUSIONS: Despite the high atherogenic potential of altered lipid metabolism found in hFH, the prevalence of CAD is similarly increased in patients with hFH or FCH. This may be related to the clustering of non-lipid cardiovascular risk factors, such as diabetes mellitus, observed in patients with FCH.

Adult↗
PubMed2006

Nitric oxide-releasing aspirin: will it say NO to atherothrombosis?

Aspirin is a powerful anti-platelet drug widely used in patients with coronary atherosclerosis, but its side effects and especially its toxicity for gastrointestinal tract limit its usefulness in specific groups of patients. A new category of agents, nitric oxide-releasing aspirins (such as NCX-4016), seems to provide an alternative solution. Although this drug is still at phase II clinical trials, it has provided promising results until now. When administered in vivo, it is separated into an aspirin moiety and an NO-donating complex, providing both the antithrombotic effect of aspirin and the gastroprotective effect of NO. Additionally, it increases NO bioavailability as a vascular level, and it may have the antiatherogenic properties of endogenously produced NO. Finally, recent evidence suggests that it may also improve functional aspects of vein grafts used in CABG, with possible benefit on graft patency. However, the outcome of the large ongoing trials is needed before any conclusion is made about the role of NO-releasing aspirins in cardiovascular disease.

Aspirin↗
PubMed2006

5-methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels: effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling.

BACKGROUND: The circulating form of folic acid, 5-methyltetrahydrofolate (5-MTHF), may have beneficial effects on endothelial function; however, its mechanisms of action remain uncertain. Decreased nitric oxide (NO) bioavailability and increased vascular superoxide production in vascular disease states are due in part to endothelial NO synthase (eNOS) uncoupling related to deficiency of the eNOS cofactor tetrahydrobiopterin (BH4), but whether this mechanism is important in human atherosclerosis and represents a rational therapeutic target remains unclear. We hypothesized that 5-MTHF would improve endothelial function by decreasing superoxide and peroxynitrite production and by improving eNOS coupling, mediated by BH4 availability. METHODS AND RESULTS: Vascular superoxide/peroxynitrite production and vasomotor responses to acetylcholine and bradykinin were determined in saphenous veins and internal mammary arteries from 117 patients undergoing CABG. The effects of 5-MTHF were examined ex vivo (n = 61) by incubating vessels with 5-MTHF (1 to 100 micromol/L) and in vivo by intravenous infusion of 5-MTHF or placebo before vessel harvest (n = 56). 5-MTHF improved NO-mediated endothelium-dependent vasomotor responses and reduced vascular superoxide, both ex vivo and in vivo. These changes were not explained by direct superoxide scavenging by 5-MTHF in vitro or by changes in plasma total homocysteine in vivo. Rather, 5-MTHF was a strong peroxynitrite scavenger and increased vascular BH4 and the BH4/total biopterin ratio. Furthermore, 5-MTHF reversed eNOS uncoupling, as assessed by NG-nitro-l-arginine methyl ester-inhibitable superoxide production, increased the eNOS dimer:monomer ratio, and enhanced eNOS activity. CONCLUSIONS: 5-MTHF has beneficial effects on endothelial function and vascular superoxide production in human atherosclerosis, by preventing peroxynitrite-mediated BH4 oxidation and improving eNOS coupling.

Acetylcholine↗
PubMed2006

Potential role of endothelial progenitor cells in the pathophysiology of heart failure: clinical implications and perspectives.

Endothelial dysfunction is thought to play a major role in the development and clinical complications of heart failure. Endothelial progenitor cells (EPCs) have been shown to provide an endogenous repair mechanism to counteract detrimental risk factor-induced effects and replace dysfunctional endothelium. The number and in vitro function of EPCs is altered in patients with heart failure, as a result of its pathophysiological mechanisms. EPCs could represent a substitutional marker to guide preventive or therapeutic interventions in this disease. Enhancing the number and functional capacity of EPCs with targeted interventions may elicit functional improvement in individuals with heart failure. However, the exact role of EPCs in heart failure and their potential therapeutic implications still remain to be elucidated.

Animals↗
PubMed2006

L-Arginine, the substrate for NO synthesis: an alternative treatment for premature atherosclerosis?

L-Arginine is the substrate of endothelial nitric oxide synthase (eNOS) and the main precursor of nitric oxide (NO) in the vascular endothelium. L-Arginine improves endothelial function in patients with hypercholesterolemia, hypertension and smokers, while its role in diabetes remains unclear. Oral supplementation of L-arginine leads to a significant improvement of endothelium-dependent forearm vasodilation in hypercholesterolemic patients, while intravenous infusion of L-arginine improves endothelial function in healthy smokers. L-Arginine has anti-hypertensive properties, although its effects on endothelial function in hypertensive patients needs further evaluation. In conclusion, L-arginine administration may be useful in patients with premature atherosclerosis.

Age Factors↗
PubMed2006

Differences in inflammatory and thrombotic markers between unstable angina and acute myocardial infarction.

BACKGROUND: Unstable coronary syndromes are characterised by increased inflammatory process and endothelial activation. However, the underlying mechanisms of the acute coronary syndromes are still obscure. We evaluated the differences of inflammatory and thrombotic markers, at the acute phase of unstable angina (UA) and acute myocardial infarction (AMI). METHODS: The population of the study consisted of 216 subjects: 136 patients with UA, 57 patients with AMI and 23 healthy controls. Blood samples were taken by their admission to the hospital. Inflammatory and thrombotic markers were measured by ELISA. RESULTS: Patients with UA had significantly higher levels of interleukin-6 (IL-6), soluble vascular cells adhesion molecule (sVCAM-1) and von Willebrand factor (vWF) (p<0.05 vs controls), and lower levels of antithrombin III (ATIII) (p<0.01 vs controls) and protein C (PrtC) (p<0.05 vs controls). Similarly, patients with AMI had higher levels of IL-6, sVCAM-1, vWF and tissue plasminogen activator (tPA) (p<0.01 vs controls) and lower levels of ATIII (p<0.01 vs controls) and prtC (p<005 vs controls). Patients with AMI had significantly higher levels of vWF, tPA and sVCAM-1 compared to UA patients (p<0.05). CONCLUSIONS: Patients with unstable coronary syndromes had increased levels of IL-6, sVCAM-1 and vWF as well as decreased levels of ATIII and PrtC by their admission. However, patients with AMI had higher levels of all the endothelium-derived inflammatory (e.g. sVCAM-1) of thrombotic/fibrinolytic (e.g. tPA and vWF) markers, compared to those with UA. These findings imply that patients with myocardial infarction show further increase of endothelium-derived inflammatory and thrombotic markers compared to patients with unstable angina, in response to a similar proinflammatory stimuli.

Angina, Unstable↗
PubMed2006

Pro-inflammatory cytokines in acute coronary syndromes: from bench to bedside.

Cytokines are produced in a variety of tissues and regulate the expression of a number of inflammatory molecules, leading to destabilization and finally rupture of vulnerable atheromatic plaques. They also participate in the pathophysiology of acute coronary syndromes (ACS) by direct effects on myocardial contractility and apoptosis. At a clinical level, circulating cytokines have a prognostic role since they are useful markers predicting future coronary events in patients with advanced atherosclerosis and in patients after ACS.

Acute Disease↗
PubMed2006

Long-term effects of levosimendan infusion on inflammatory processes and sFas in patients with severe heart failure.

BACKGROUND: The calcium sensitizer levosimendan improves myocardial contractility in patients with heart failure, although its effects on inflammation and apoptosis are unknown. AIM: To examine the effects of levosimendan on markers of inflammation and apoptosis, over a period of 30 d following a 24 h infusion, in patients with heart failure. METHODS: Thirty four patients with severe heart failure were randomised to receive a 24 h infusion of levosimendan or placebo, in a double-blind trial. Haemodynamic evaluation and blood sampling were performed at baseline, 24 h, 30 h, 48 h, 7 d and 30 d after the end of the infusion. RESULTS: Seven patients (1 levosimendan, 6 placebo), were excluded during follow-up. In the remaining 27 patients, levosimendan decreased serum IL-6 and sFAS, 24 h after the infusion (p<0.01 and p<0.05 vs baseline), an effect sustained for 7-30 d. Serum TNF-alpha and sTNF-R1 were decreased between 48 h (p<0.01 vs baseline for both) and 7 d (p<0.05 vs baseline for sTNF-R1) after infusion. Serum sTNF-R2 was decreased at 24 h (p<0.05 vs baseline) and remained lower than baseline for at least 7 d (p<0.05). CONCLUSIONS: These findings indicate that levosimendan decreases the expression of proinflammatory cytokines, TNF-alpha receptors and sFAS, immediately after infusion, an effect which persists for 7-30 d.

Aged↗
PubMed2006

Genetic polymorphisms of platelet glycoprotein Ia and the risk for premature myocardial infarction: effects on the release of sCD40L during the acute phase of premature myocardial infarction.

OBJECTIVES: The aim of this research was to evaluate the effect of genetic polymorphisms C807T and G1648A of platelet glycoprotein Ia (GPIa), on the risk for myocardial infarction (MI) and on the release of soluble CD40 ligand (sCD40L) during the acute phase of MI and one year after the event. BACKGROUND: C807T and G1648A polymorphisms affect the density of GPIa on platelet surface, but their effect on the risk for MI and the release of sCD40L is unknown. METHODS: The study population consisted of 219 patients with premature MI and 389 controls. One year after the event, 67 patients and 232 controls were recalled for the follow-up study. RESULTS: The risk for MI in 807TT was 2.296 (95% confidence interval [CI]: 1.187 to 4.440) p < 0.05 versus CC + CT, 2.269 (95% CI: 1.085 to 4.745) p < 0.05 versus CC, and 2.135 (95% CI: 1.080 to 4.219) p < 0.05 versus CT. During the acute phase of MI, sCD40L was higher in 807CT + TT compared with 807CC (p < 0.01), an effect persisting after one year (p < 0.01). The carriage of 807T allele was an independent predictor for sCD40L during the acute phase of MI (beta = 9.442 [standard error (SE): 2.526], p = 0.001) and in the same patients one year later (beta = 8.282 [SE: 2.044], p = 0.001). In healthy individuals, 807T allele was associated with higher sCD40L levels compared with 807CC (p < 0.05), only among those with von Willebrand factor greater than or equal to median. CONCLUSIONS: Genetic polymorphism C807T increases the risk for premature MI. 807T allele is an independent predictor for sCD40L levels during the acute phase of premature MI as well as one year after the event, while it is associated with elevated sCD40L levels in healthy subjects, only in the presence of high von Willebrand levels.

CD40 Ligand↗
PubMed2006

Genetic polymorphisms G894T on the eNOS gene is associated with endothelial function and vWF levels in premature myocardial infarction survivors.

BACKGROUND: Genetic polymorphism G894T on endothelial nitric oxide synthase (eNOS) gene has been associated with endothelial dysfunction in young smokers, but its role in the pathogenesis of MI is obscure. We examined the effect of G894T polymorphism on endothelial function, on markers of endothelial cells injury and activation such as von Willebrand factor (vWF) and on serum levels of proinflammatory cytokines such as interleukins 6 (IL-6) and 1b (IL-1b), in young myocardial infarction (MI) survivors. METHODS: The study population consisted of 56 patients with a history of premature MI. The forearm blood flow (FBF) was measured by using strain-gauge plethysmography during reactive hyperemia and after sublingual administration of nitroglycerin. G894T polymorphism was determined by polymerase chain reaction (PCR), while plasma vWF and serum IL1b and IL-6 levels were determined with ELISA. RESULTS: There was no significant difference in resting FBF and in the responses to nitroglycerin between the genotypes. However, the presence of T allele (GT+TT, n=35) was associated with decreased FBF during reactive hyperemia (10.23+/-0.70 ml/100ml tissue/min) and decreased forearm vasodilatory response to reactive hyperemia (54.28+/-4.81%) compared to GG (13.82+/-0.92 ml/100 ml tissue/min and 83.92+/-9.89% respectively, p<0.01 for both). Carriers of the T allele had also higher levels of vWF (79.66+/-5.56%) compared to GG (60.94+/-5.27% p<0.05). However, no significant difference was observed in IL-1b and IL-6 serum levels between the genotypes (p=ns for both). CONCLUSIONS: The presence of 894T allele on eNOS gene is associated with impaired endothelial function and higher levels of von Willebrand factor in relatively young patients with myocardial infarction. This finding implies that genetic polymorphism G894T on eNOS may affect endothelial function in patients with a history of premature myocardial infarction.

Alleles↗
PubMed2006

Effects of early administration of atorvastatin treatment on thrombotic process in normocholesterolemic patients with unstable angina.

BACKGROUND: Although statin-treatment during the acute phase of unstable coronary syndromes improve the outcome their effects on thrombosis/fibrinolysis system in normocholesterolemic patients admitted with unstable angina remain obscure. We assessed the effects of short-term atorvastatin treatment on thrombotic/fibrinolysis markers in normocholesterolemic in patients with unstable angina. METHODS: Forty-five patients with unstable angina were allocated into two groups to receive atorvastatin 10 mg/day (n = 24) or no statin (n = 21) for 6 weeks. Circulating levels of von Willebrand Factor (vWF), factor V (fV), protein C (prC), tissue plasminogen activator (tPA) and antithrombin III (ATIII) were measured by enzyme linked immunosorbent assay, by the patients admission and at the 1st and 6th week of the study. RESULTS: After 1 week of treatment, a significant increase of ATIII (p < 0.05), fV (p < 0.01) and vWF (p < 0.05) was found in the control group, but not in atorvastatin-treated group. Similarly, at 6 weeks after admission, plasma levels of ATIII were still significantly higher than at baseline in controls (p < 0.05), but not in atorvastatin-treated group. Plasma levels of PrtC were significantly increased in both controls (p < 0.01) and atorvastatin-treated patients (p < 0.05) at 1 week, while remained unaffected in atorvastatin-treated group at 6th week. There was no significant difference in the variations of plasma levels of tPA, PrtS and fVII between the two groups at 1 and 6 weeks after admission. CONCLUSIONS: In normocholesterolemic patients admitted with unstable angina the early administration of atorvastatin, significantly affects von Willebrand factor levels and the expression of liver-derived components of both thrombosis and fibrinolysis system.

Angina, Unstable↗
PubMed2006

Acute improvement of aortic mechanics following hemodialysis in patients with chronic renal failure.

BACKGROUND: Evidence suggests that distensibility of the aorta is decreased in patients with end-stage renal failure, while the underlying mechanisms are unclear. HYPOTHESIS: The purpose of the study was to evaluate the distensibility of the aorta in patients at the end stage of chronic renal failure before and after hemodialysis (HD). METHODS: The diameter of the ascending aorta and distensibility were assessed in 48 patients on HD (31 men, 17 women, aged 45+/-14 years) and in 27 normal subjects (17 men, 10 women, aged 44+/-14 years). The diameter of the aorta was evaluated by M-mode in the parasternal long-axis view. RESULTS: Aortic distensibility was significantly lower in patients on HD before HD (1.9+/-0.7 cm(2) x dyn(-1) x 10(-6)) than in normal control subjects (3.8+/-1.0 cm(2) x dyn(-1) X 10(-6), p< 0.0001). After dialysis, it increased to 2.6+/-1.2 (p < 0.05 compared with baseline, p < 0.001 compared with controls). The change of aortic distensibility correlated with age (R(2) = 0.629 p < 0.001) and ultrafiltration volume (R(2) = 0.168, p < 0.01). CONCLUSIONS: Aortic distensibility in patients with end-stage renal disease is significantly lower than in normal subjects, and it is significantly improved after HD.

Acute Disease↗
PubMed2006

Asymmetrical dimethylarginine regulates endothelial function in methionine-induced but not in chronic homocystinemia in humans: effect of oxidative stress and proinflammatory cytokines.

BACKGROUND: Homocystinemia is a metabolic abnormality associated with endothelial dysfunction and increased cardiovascular disease risk. The underlying mechanisms of these effects, however, are obscure. OBJECTIVE: We examined the effect of asymmetrical dimethylarginine (ADMA) on endothelial dysfunction in methionine-induced and chronic homocystinemia and evaluated the regulatory role of oxidative stress and proinflammatory cytokines on the release of ADMA. DESIGN: In this double-blind, placebo-controlled parallel group study, 30 subjects of both sexes (15 with homocystinemia and 15 healthy controls) underwent methionine loading, with simultaneous administration of a combination of vitamin C (2 g) plus alpha-tocopherol (800 IU) or placebo. Endothelial function in forearm resistance vessels and concentrations of ADMA, oxidized LDL, and proinflammatory cytokines were determined at baseline and 4 h after methionine loading. RESULTS: Both chronic and methionine-induced homocystinemia were associated with increased oxidized LDL (P < 0.01), higher expression of the proinflammatory cytokine interleukin 6 (P < 0.05), and endothelial dysfunction (P < 0.01). Although ADMA rapidly increased in acute homocystinemia (P < 0.01) and was correlated with forearm hyperemic response at 4 h after methionine loading (r = -0.722, P = 0.0001), it was not higher in subjects with high versus low fasting homocysteine. High-dose antioxidant treatment prevented methionine-induced elevation of oxidized LDL and interleukin 6 but failed to prevent the increase in ADMA or endothelial dysfunction. CONCLUSIONS: Both chronic and methionine-induced homocystinemia are characterized by increased oxidative stress and proinflammatory cytokines, which may contribute to the development of endothelial dysfunction. However, the ADMA pathway is activated only in acute homocystinemia by mechanisms not mediated by oxidized LDL or proinflammatory stimuli.

Adult↗
PubMed2005

Endothelial dysfunction and inflammatory process in transfusion-dependent patients with beta-thalassemia major.

BACKGROUND: Beta-thalassemia major is associated with increased cardiovascular risk, although the underlying mechanisms remain unclear. We examined endothelial function and serum levels of inflammatory mediators in transfusion-dependent patients with beta-thalassemia major. METHODS: The study population consisted of 67 patients with homozygous beta-thalassemia major, (aged 24.6+/-0.7 years) and 71 healthy age and sex matched controls. Forearm blood flow was measured with gauge-strain plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to nitrate (NTG%) was expressed as the percentage change of forearm blood flow from baseline to the maximum flow during reactive hyperemia or sublingual nitroglycerin, respectively. Serum levels of interleukin 6 (IL-6), soluble vascular cell adhesion molecule (sVCAM-1) and soluble intercellular adhesion molecule (sICAM-1) were determined with ELISA. RESULTS: Patients had significantly lower levels of total cholesterol (125+/-4.5 vs. 207+/-7 mg/ml, p<0.01), ApoA1 (120+/-3 vs. 129+/-5 mg/ml, p<0.05), ApoB (60.5+/-2 vs. 95+/-4 mg/ml, p<0.01), ApoE (3+/-2 vs. 4+/-0.2 mg/ml, p<0.01) and Lp(a) (7.9+/-1.3 vs. 14.5+/-3.2 mg/ml, p<0.01) than controls. IL-6 levels were significantly higher in patients (3.03+/-0.31 pg/ml) than controls (1.15+/-0.15 pg/ml, p<0.01). Similarly, sVCAM-1 and sICAM-1 levels were significantly higher in patients (513+/-31 and 368+/-25.5 ng/ml, respectively) than controls (333+/-13.8 and 272+/-14.05 ng/ml, respectively, p<0.01 for both). Maximum hyperemic forearm blood flow and RH% were lower in patients (7.1+/-0.3 ml/100 ml tissue/min and 49+/-2.8%, respectively) than controls (8.26+/-0.32 ml/100 ml tissue/min and 86.3+/-5.57%, respectively, p<0.01 for both). CONCLUSIONS: Beta-thalassemia major is associated with impaired endothelial function and increased levels of IL-6, sVCAM-1 and sICAM-1, suggesting a potential role of inflammation and endothelial dysfunction in the complications of the disease.

Apolipoprotein A-I↗