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Dimitris Tousoulis

Publications and source records attributed to Dimitris Tousoulis.

47 records · Page 3Linked to original sources
PubMed2003

Oxidative stress, antioxidant vitamins, and atherosclerosis. From basic research to clinical practice.

Oxidative stress is involved in the pathogenesis of atherosclerosis, while a variety of antioxidants has been used in clinical studies, during the past few years, for the prevention and treatment of atherosclerosis. In small clinical studies it was found that both vitamins C and E may improve endothelial function in patients with risk factors for atherosclerosis such as diabetes mellitus, smoking, hypertension, or hypercholesterolemia. However, the initial, hopeful reports regarding the beneficial role of antioxidant vitamins against atherosclerosis, derived from purely observational studies, were followed by the negative results of almost all large randomized trials. Therefore, treatment with antioxidant vitamins C and E should not be recommended for the prevention or treatment of coronary atherosclerosis. New antioxidant strategies are needed to clarify the exact role of antioxidant treatment in coronary atherosclerosis.

Adult↗
PubMed2003

Effects of combined administration of vitamins C and E on reactive hyperemia and inflammatory process in chronic smokers.

Purpose of this study was to investigate the effect of combined administration of antioxidant vitamins C and E on endothelial function and serum levels of inflammatory markers such as tumor necrosis factor alpha (TNF-alpha), interleukines 1b (IL-1b) and 6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin in chronic smokers. Forty-three smokers were randomly divided into four groups receiving vitamin C 2 g/day (group A), vitamin C 2 g/day plus vitamin E 400 IU/day (group B), vitamin C 2 g/day plus vitamin E 800 IU/day (group C) or no antioxidant treatment (group D), for 4 weeks. Forearm blood flow (FBF) was measured using venous occlusion strain gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) was expressed as the percentage change from baseline to post reactive hyperemia blood flow. RH% was significantly increased in groups B (P<0.05) and C (P<0.01), but remained unaffected in groups A and D. Serum levels of IL-1b, IL-6, sVCAM-1 and sICAM-1 were significantly reduced in group C (P<0.05, respectively), but remained unaffected in groups A, B and D. Thus, short term administration of vitamins C (2 g/day) and E (800 IU/day) reduces serum levels of IL-1b, IL-6, sVCAM-1 and sICAM-1, and improves forearm vasodilatory response to reactive hyperemia in healthy young smokers, while monotherapy with vitamin C alone is ineffective.

Adult↗
PubMed2003

Vitamin C affects thrombosis/ fibrinolysis system and reactive hyperemia in patients with type 2 diabetes and coronary artery disease.

OBJECTIVE: To examine the effect of vitamin C on forearm vasodilatory response to reactive hyperemia and on plasma level of plasminogen activator inhibitor 1 (PAI-1), von Willebrand factor (vWF), tissue plasminogen activator (tPA), antithrombin III (ATIII), proteins C and S, and factors V (fV) and VII (fVII) in patients with both type 2 diabetes and CAD. RESEARCH DESIGN AND METHODS: A total of 39 patients with type 2 diabetes and CAD were divided into two groups and received vitamin C (2 g/day) or no antioxidant for 4 weeks. Forearm blood flow was determined using venous occlusion gauge-strain plethysmography at baseline and after treatment. Forearm vasodilatory response to reactive hyperemia (RH%) or nitrate (NTG%) was defined as the percent change of flow from baseline to the maximum flow during reactive hyperemia or after administration of nitrate, respectively. Biochemical markers were determined by enzyme-linked immunosorbent assay (ELISA) or other standard methods. RESULTS: RH% was significantly increased after treatment with vitamin C (from 62.4 +/- 7.2 to 83.1 +/- 9.3%, P = 0.024) but remained unaffected in the control group. Vitamin C decreased plasma levels of fV (from 143 +/- 5.4 to 123 +/- 6.03%, P = 0.038), vWF (from 133.5 +/- 14.5 to 109.5 +/- 11.4%, P = 0.016), and tPA (from 12.3 +/- 0.99 to 8.40 +/- 0.60 ng/ml, P = 0.001), whereas these levels remained unaffected in the control group. The changes in RH%, vWF, and tPA were significantly greater (P = 0.028, 0.036, and 0.007, respectively) in the vitamin C-treated group than in the control group. Levels of ATIII, proteins S and C, fVII, and PAI-1 remained unchanged in all groups. CONCLUSIONS: Short-term treatment with high doses of vitamin C improved RH% and decreased plasma levels of tPA and vWF in patients with type 2 diabetes and CAD.

Administration, Oral↗
PubMed2003

The impact of platelet glycoprotein IIIa and Ia polymorphisms in cardiovascular thrombotic disease.

Platelet adhesion and aggregation play key roles in initiating coronary thrombosis and acute coronary syndromes. During the last decade platelet glycoprotein Ia and IIIa polymorphisms have been studied intensely in order to clarify their contribution to the thrombotic process and moreover their role in acute coronary syndromes. Studies examining these polymorphisms have been inconclusive and often controversial. Polymorphisms in the glycoprotein Ia seem to increase the risk for acute coronary events in younger persons and especially in the presence of other risk factors. The correlation of the Leu33Pro allele of platelet glycoprotein IIIa regarding platelet thrombogenicity is strong but it does not seem to alter the thrombotic risk of the general population. In conclusion, further studies need to elucidate their impact and the potential association with acute thrombotic events.

Adult↗
PubMed2003

Effects of antioxidant vitamins C and E on endothelial function and thrombosis/fibrinolysis system in smokers.

Smoking is associated with endothelial dysfunction and abnormalities in thrombosis/fibrinolysis system, possibly through increased oxidative stress. In this study we investigated the effect of combined antioxidant treatment with vitamins C and E on endothelial function and plasma levels of plasminogen activator inhibitor (PAI-1), von Willebrand factor (vWF), tissue plasminogen activator (tPA) and factor VII (fVII), in smokers. Forty-one healthy smokers were randomly divided into 4 groups receiving vitamin C 2g/day (group A), vitamin C 2g/day plus vitamin E 400 IU/day (group B), vitamin C 2g/day plus vitamin E 800 IU/day (group C) or no antioxidants (controls, group D), for 4 weeks. Forearm blood flow was measured using venous occlusion strain-gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to sublingual nitroglycerin administration (NTG%) were considered as indexes of endothelium dependent or independent dilation respectively. After treatment, RH% was increased only in groups B (p <0.05) and C (p <0.001) but not in groups A and D. Plasma levels of PAI-1 and vWF were decreased only in group C (p <0.05 for both), while PAI-1/tPA ratio was significantly decreased in both groups B and C (p <0.05 for both). NTG% and plasma levels of tPA and fVII remained invariable in all groups. In conclusion, combined administration of vitamin C and vitamin E at high dosages, improved endothelial function and decreased plasma levels of PAI-1, vWF and PAI-1/tPA ratio in chronic smokers.

Adult↗
PubMed2002

Basic fibroblast growth factor changes in response to coronary angioplasty in patients with stable angina.

Basic fibroblast growth factor (bFGF) has been implicated in the pathogenesis of coronary atherosclerosis and in angiogenesis. We assessed the changes in serum bFGF before, immediately after, and 6 months after coronary angioplasty (PTCA). Using the ELISA methods we measured plasma bFGF in 28 patients who underwent PTCA, in 20 patients with coronary artery disease who underwent elective coronary angiography and in 28 healthy subjects. Before PTCA and coronary angiography, bFGF plasma levels were similar in both patient groups (4.4+/-1.0 vs. 3.3+/-0.5 pg/ml), but were significantly higher compared with those of the control group (0.8+/-0.1 pg/ml, P<0.05). By 24 h, 3 months and 6 months after PTCA, bFGF levels had decreased significantly in the PTCA group (3.2+/-0.6, 1.7+/-0.3 and 2.7+/-0.6 pg/ml, respectively, P<0.05). In conclusion, these findings show that bFGF levels are elevated in patients with coronary artery disease. Following PTCA, bFGF levels decreased significantly and remained stable for 6 months after the procedure. Thus, bFGF level may change in response to PTCA in patients with coronary artery disease and stable angina.

Aged↗
PubMed2002

Effects of lipids on thrombotic mechanisms in atherosclerosis.

Cholesterol lowering therapy markedly reduces the frequency of subsequent cardiovascular events and is associated with a modest degree of angiographic regression of atherosclerotic lesions. There is a strong association between lipids and fibrinogen, plasminogen activator-1, and activated factor VII levels. Low density lipoprotein may be thrombogenic whereas high density lipoprotein protects against thrombosis. Lipoprotein (a) may affect atherosclerosis and thrombosis mainly by binding to fibrin and attenuating the fibrin-enhanced plasminogen activation. Tissue factor-complex initiates coagulation by activating factor X and factor IX leading in the presence of calcium to the generation of thrombin. Lipid lowering treatment with statins stabilizes atheromatous plaque and has antithrombotic effects. Therefore there are links between lipids and the haemostatic mechanisms which affect atherosclerotic, vasomotor and thrombotic components of ischemic heart disease.

Arteriosclerosis↗
PubMed2002

L-arginine in cardiovascular disease: dream or reality?

L-arginine is the substrate for endothelial nitric oxide synthase (eNOS), and the precursor for the synthesis of nitric oxide (NO). This amino acid exerts a number of actions in the cardiovascular system, mainly through the production of NO. However, it also has a number of NO-independent properties, such as the ability to regulate blood and intracellular pH and the effect on the depolarization of endothelial cell membranes. It also has antihypertensive and antioxidant properties, it influences blood viscosity and the coagulation/fibrinolysis system, and it affects the metabolism of glucose, lipids and proteins. L-arginine influences a number of atherosclerosis risk factors such as hypercholesterolemia, hypertension and smoking, improving endothelial function in these patients. However, it does not affect endothelial function in patients with diabetes mellitus. The role of L-arginine in coronary artery disease is still controversial, but it seems that oral or parenteral administration of this amino acid restores endothelial function in the brachial artery and improves coronary microcirculation. The role of L-arginine in heart failure is currently under investigation, and the first results are rather hopeful. In conclusion, L-arginine seems to provide a hopeful prospect for the treatment of cardiovascular diseases. However, more data derived from large-scale prospective studies evaluating the effects of long-term treatment with L-arginine are needed.

Animals↗
PubMedDate not supplied

Novel therapies targeting vascular endothelium.

Endothelial dysfunction has been identified as a major mechanism involved in all the stages of atherogenesis. Evaluation of endothelial function seems to have a predictive role in humans, and therapeutic interventions improving nitric oxide bioavailability in the vasculature may improve the long-term outcome in healthy individuals, high-risk subjects, or patients with advanced atherosclerosis. Several therapeutic strategies are now available, targeting both the synthesis and oxidative inactivation of nitric oxide (NO) in human vasculature. Statins seem to be currently the most powerful category of these agents, improving endothelial function and decreasing cardiovascular risk after long-term administration. Other cardiovascular agents improving endothelial function in humans are angiotensin-converting enzyme inhibitors/angiotensin receptors blockers, which increase NO bioavailability by modifying the rennin-angiotensin-aldosterone system. Newer therapeutic approaches targeting endothelial dysfunction in specific disease states include insulin sensitizers, L-arginine (the substrate for endothelial NO synthase [eNOS]) as well as substances that target eNOS "coupling," such as folates or tetrahydrobiopterin. Although there are a variety of strategies to improve NO bioavailability in human endothelium, it is still unclear whether they have any direct benefit at a clinical level.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Effects of lipid profile on forearm hyperemic response in young subjects.

INTRODUCTION: The role of lipids in atherogenesis is now well established. However, the exact mechanisms by which different lipoproteins affect endothelial function and induce atherogenesis are still not well understood. In the present study we examined the effect of lipid profile on forearm vasodilatory response to reactive hyperemia, an index of endothelial function, in a cohort of young, low-risk adults. METHODS: One hundred sixty seven healthy subjects were included in the study. The effect of total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, apolipoprotein (apo)-A1, apo-B and apo-E on endothelial function and inflammatory process was examined. Endothelial function was evaluated by determining forearm vasodilatory response to reactive hyperemia (RH%) using gauge-strain plethysmography. RH% was defined as the % change of forearm blood flow from baseline to the maximum flow during post-ischemic hyperemia. Endothelium independent dilatation in response to nitroglycerin (NTG%) was defined as the % change of forearm blood flow from baseline to the maximum flow after sublingual nitroglycerin administration. RESULTS: RH% was correlated with HDL (r = 0.267, p = 0.001), LDL (r = 0.355, p = 0.0001), triglycerides (rho = -0.366, p = 0.0001), apo-Al (r = 0.240, p = 0.004) and apo-B (r = -0.277, p = 0.005). NTG% was not affected by serum lipid levels. In multivariate linear regression, LDL (beta = -0.217 [SE: 0.098], p = 0.028), apo-A1 (beta = 0.277 [SE: 0.124], p = 0.027) and age (beta = 0.916 [SE:0.369], p = 0.015) were independent predictors for RH% in this population (R2 for the model: 0.243, p = 0.0001). CONCLUSIONS: Elevated lipid levels decrease forearm vasodilatory response to reactive hyperemia. Apolipoproteins, and especially apo-Al, are important determinants of endothelial function in these subjects, independently of LDL, HDL and triglycerides, implying that full measurement of the lipid profile may be of great importance in risk stratification of young individuals.

Adult↗