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Cardiovascular disease, which is multifactorial and can be influenced by a multitude of environmental and heritable risk factors, remains a major health problem, even though its pathophysiology is far from been elucidated. Discovered just over a decade ago, microRNAs comprise short, non-coding RNAs, which have evoked a great deal of interest, due to their importance for many aspects of homeostasis and disease. Hundreds of different microRNAs are constantly being reported in various organisms. According to a growing body of literature, they have been implicated in the regulation of human physiological processes. More specifically, miRNAs are expressed in the cardiovascular system and could have crucial roles in normal development and physiology, as well as in disease development. Furthermore, they have been shown to participate in cardiovascular disease pathogenesis including atherosclerosis, coronary artery disease, myocardial infarction, heart failure and cardiac arrhythmias. In contrast to our original thought, miRNAs exist in circulating blood and are relatively stable, thus, they could be proved useful as biomarkers in that state. Understanding the underlying mechanisms, in which these major regulatory gene families are implicated, will provide novel opportunities for diagnosis and therapy of cardiovascular diseases.

Cardiovascular disease, which is multifactorial and can be influenced by a multitude of environmental and heritable risk factors, remains a major health problem, even though its pathophysiology is far from been elucidated. Discovered just over a decade ago, microRNAs comprise short, non-coding RNAs, which have evoked a great deal of interest, due to their importance for many aspects of homeostasis and disease. Hundreds of different microRNAs are constantly being reported in various organisms. According to a growing body of literature, they have been implicated in the regulation of human physiological processes. More specifically, miRNAs are expressed in the cardiovascular system and could have crucial roles in normal development and physiology, as well as in disease development. Furthermore, they have been shown to participate in cardiovascular disease pathogenesis including atherosclerosis, coronary artery disease, myocardial infarction, heart failure and cardiac arrhythmias. In contrast to our original thought, miRNAs exist in circulating blood and are relatively stable, thus, they could be proved useful as biomarkers in that state. Understanding the underlying mechanisms, in which these major regulatory gene families are implicated, will provide novel opportunities for diagnosis and therapy of cardiovascular diseases. © 2012 Bentham Science Publishers.

Atherosclerosis is a very complex procedure responsible for the development of coronary artery disease which is the leading cause of death in the civilized world. The obvious pandemic character of atherosclerosis augments the need to discover an ideal biomarker, which will be able to facilitate the clinical diagnosis of the atherosclerosis from the physicians especially in the early stages of the atherosclerotic process. Among the biomarkers that are already used there are classical ones, such as c-reactive protein, interleukins, tumour necrosis factor, apolipoproteins, fibrinogen, homocysteine, and novel promising ones such as lipoprotein-associated phospholipase, asymmetric dimethylarginine, myeloperoxidase, cathepsins and cystatin C. The possibility of combining circulating biomarkers with other methods such as non-invasive and invasive imaging is clinically attractive because this could contribute to the improved diagnosis and understanding of premature atherosclerosis pathogenesis. © 2012 Bentham Science Publishers.

The authors sought to investigate whether serum uric acid levels are associated with systolic left and right ventricular function, as well as left atrial function in patients with newly diagnosed heart failure. The authors enrolled 106 consecutive patients (mean age 65±13 years). Echocardiographic and biochemical assessment was performed during the third day of hospitalization. Pulsed tissue Doppler imaging of the systolic function of mitral and tricuspid annulus was characterized by the systolic waves (Smv and Stv, respectively), expressed in cm/s, and the left atrial function by the Amv wave. Left atrial kinetics was calculated using an equation. Serum uric acid levels were inversely correlated with Stv (P=.005) and left atrial kinetics (P=.05), after controlling for potential confounders. Uric acid levels appear to be correlated with more impaired right ventricular systolic function and decreased left atrial work in patients with heart failure. Congest Heart Fail. © 2008 Le Jacq.

Background: Genetic polyinorphism 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-lb), 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 Tallele 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-lb 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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Background: Heart failure has been associated with impaired endothelial function, increased inflammatory process and elevated oxidative stress status. Both statins and vitamin E separately improve endothelial function in patients with hypercholesterolemia and/or advanced atherosclerosis. Aim: To evaluate the effect of atorvastatin alone or in combination with vitamin E on endothelial function and serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and vascular cells adhesion molecule (sVCAM-1) in patients with ischemic heart failure. Methods: Thirty-eight male patients with ischemic cardiomyopathy were randomly divided into three groups and received either atorvastatin 10 mg/day (n = 14), a combination of atorvastatin 10 mg/day plus vitamin E 400 IU/day (n = 12), or no statin or antioxidant treatment (n = 12, controls) for 4 weeks. Forearm blood flow (FBF) was measured using venous occlusion strain-gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to nitrate (NTG%) was defined as the percent change of FBF from rest to the maximum flow during reactive hyperemia or after nitrate administration, respectively. Results: RH% was significantly improved in both the atorvastatin-treated (p < 0.0 1) and atorvastatin plus vitamin E groups (p < 0.05), but the increase was significantly higher in the atorvastatin-treated group (p < 0. 05). Serum levels of IL-6, TNF-alpha and sVCAM-1 were decreased in the atorvastatin-treated group (p < 0.05 for all), but remained unaffected in the other two groups (p =NS for all). Conclusions: Low dose atorvastatin treatment improves endothelial ftinction and reduces the expression of proinflammatory cytokines and adhesion molecules in patients with ischemic heart failure, an effect partly depressed by vitamin E. (c) 2005 European Society of Cardiology. Published by Elsevier B.V All rights reserved.

Objective: To assess the effects of intravenous vitamin C administration on the vasomotor responses to intracoronary L-arginine infusion in epicardial coronary arteries. Methods: 28 patients with coronary artery disease and stable angina were enrolled in the study. Eight patients received intracoronary infusions of 150 mmol/min L-arginine before and after intravenous infusion of vitamin C, 10 patients received intracoronary infusions of 150 mu mol/min L-arginine before and after intravenous infusion of normal saline, and 10 patients received intracoronary normal saline before and after intravenous infusion of vitamin C. The diameter of proximal and distal coronary artery segments was measured by quantitative angiography. Results: Infusion of L-arginine caused significant dilatation of both proximal (4.87(0.96)%, p

OBJECTIVES This study sought to evaluate the effect of genetic polymorphism G894T on endothelial nitric oxide synthase (eNOS); on the risk for myocardial infarction (MI); and on the release of von Willebrand factor (vWF), interleukin (IL)-6, IL-1b, and oxidized low-density lipoprotein (ox-LDL) levels during the acute phase of MI and one year after the event. BACKGROUND Genetic polymorphism G894T on eNOS has been associated with increased cardiovascular risk. However, its role during the acute phase of MI is unknown. METHODS The study population consisted of 228 patients with a first event of premature MI and 519 matched control patients. One year after the event, 61 patients and 205 control patients were recalled for the follow-up study. Blood sampling was performed during the acute phase and after one year. RESULTS The risk for MI in 894TT was 1.992 (95% confidence interval [Cl], 1.131 to 3.485), p < 0.05 versus GG+GT; 2.038 (95% CI, 1.125 to 3.695), p < 0.05 versus GG; and 2.009 (95% Cl, 1.106 to 3.651), p < 0.05 versus GT. During the acute phase, vVVF was higher in GT+TT (121.02 +/- 5.47%) versus GG (84.6 +/- 7.1%, p < 0.01), an effect persisting after one year (90.4 +/- 3.8 vs. 73.1 +/- 4.6%, p < 0.01). During the acute phase, GT+TT had higher ox-LDL and IL-6 (131.2 +/- 6.4 IU/l and 8.5 +/- 0.7 pg/ml) compared with GG (101.7 +/- 9.64 IU/l and 6.2 +/- 0.8 pg/ml, p < 0.05 for both), but no difference was found at one year. CONCLUSIONS G894T polymorphism on the eNOS gene increases the risk for premature MI and modifies the response of vascular endothelium during the acute phase,of M1 by affecting the release of vWF, IL-6, and oxidative stress status, an effect diminished one year after the event.

Objective: To investigate the effects of short term atorvastatin treatment on forearm vasodilatory response to reactive hyperaemia (RH%) and on components of the thrombosis - fibrinolysis system ( antithrombin III, proteins and S, factors V and VII, von Willebrand factor, tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI-1)) in patients with heart failure. Patients and methods: 35 patients with heart failure were enrolled in this study; 17 patients received atorvastatin 10 mg/day and 18 patients received no statin for four weeks. Forearm blood flow (FBF) was measured by venous occlusion strain gauge plethysmography. RH% and forearm vasodilatory response to nitrate were defined as the percentage change of FBF from rest to the maximum flow during reactive hyperaemia and after nitrate administration, respectively. Plasma concentrations of antithrombin III, protein C, protein S, factor V, factor VII, von Willebrand factor, tPA, and PAI-1 were determined before and after treatment. Results: Maximum hyperaemic FBF remained unchanged in both groups. Baseline FBF was slightly but not significantly decreased in the atorvastatin treated group. RH% was significantly increased only in the atorvastatin treated group, from mean (SD) 42.44 (18.9)% to 83.7 (36.1)% ( p< 0.01). Plasma concentrations of antithrombin III ( from mean (SD) 81.7 (11.37)% to 73.5 (13.8)%), protein C (from mean (SD) 88.3 (26.9)% to 63.9 (25.0)%), factor V (from mean (SD) 126.2 (33.4)% to 94.9 (29.8)%), tPA (from median (25th - 75th percentile) 11.68 ( 8.60 - 20.95) ng/ml to 10.30 (8.65 - 15.12) ng/ml), and PAI-1 ( from median ( 25th - 75th percentile) 3.10 (2.15 - 4.40) IU/l to 1.90 (0.75 - 3.0) IU/l) were significantly decreased in the atorvastatin treated group ( p< 0.05) but not in the control group. Plasma concentrations of von Willebrand factor, factor VII, and protein S remained unaffected in both groups. Conclusion: Atorvastatin did not change the maximum hyperaemic flow, although it decreased plasma concentrations of antithrombin III, protein C, factor V, tPA, and PAI-1 in patients with heart failure. Therefore, short term treatment with atorvastatin may affect the expression of both endothelium and liver derived components of the thrombosis - fibrinolysis system in patients with heart failure.

Aims Type 2 diabetes mellitus (DM) and coronary artery disease (CAD) are both associated with endothelial dysfunction and elevated oxidative and inflammatory state. We examined the effect of vitamin C on endothelial function and levels of soluble vascular cell adhesion molecule (sVCAM-1), interleukin-6 (IL-6) and tumour necrosis factor (TNF-alpha), in DM patients with or without CAD and in non-diabetic subjects. Methods Thirty-seven patients with DM + CAD, 17 patients with DM without CAD and 21 non-diabetic subjects were divided into groups receiving vitamin C 2 g/day or no anti-oxidant for 4 weeks. Forearm blood flow was determined using venous occlusion gauge-strain plethysmography. Forearm vasodilatory response to reactive hyperemia was considered as index of endothelium-dependent dilation. Results Baseline levels of IL-6 and TNF-alpha were significantly higher in patients with DM + CAD compared with patients with DM (P < 0.01) or non-diabetic subjects (P < 0.01). IL-6 and TNF-alpha levels were also higher in DM compared with non-diabetic subjects (P < 0.05). sVCAM-1 levels were lower in non-diabetic controls compared with DM + CAD (P < 0.05) or DM (P < 0.05). Reactive hyperaemia was higher in non-diabetic controls compared with DM + CAD (P < 0.001) or DM (P < 0.001). Vitamin C significantly increased reactive hyperaemia only in the DM + CAD group, while it had no effect on serum levels of sVCAM-1, TNF-alpha and IL-6 in any of the groups. Conclusions Type 2 diabetes mellitus is associated with impaired endothelial function and increased levels of TNF-alpha, IL-6 and sVCAM-1, especially in patients with DM and CAD. Vitamin C significantly increased forearm vasodilatory response to reactive hyperaemia only in patients with combined DM and CAD.

Objective: We examined the association between climatologic parameters and daily admissions for non-fatal acute coronary syndromes (ACS) to emergency units of hospitals in the greater Athens area, from January 2001 to August 2002. Methods: Daily mean, maximum and minimum temperatures, relative humidity, wind speed, barometric pressure and a thermo-hydrological index (T.H.I.) were measured at the meteorological station of the Laboratory of Climatology of the Geology Department of the University of Athens. In addition, the daily number of admissions for acute myocardial infarction or unstable angina in the five major general hospitals in the greater Athens area was recorded. Generalized additive models (GAM) were applied to regress-time-series of daily numbers of outpatients with acute cardiac events against climatological variations, after controlling for possible confounders and adjustment for over dispersion and serial correlation. Results: Five thousand four hundred fifty-eight Athenians with non-fatal acute cardiac events were admitted to the selected hospitals during the period of the study, 4093 (75%) males and 1365 (25%) females. There was a negative correlation between hospital admissions and mean daily temperature (MDT) with a I degreesC decrease in mean air temperature yielding a 5% increase in hospital admissions (P

Background: Proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) are important mediators of immune response, associated with endothelial dysfunction in patients with coronary artery disease (CAD) or heart failure. We compared endothelial function and levels of IL-6 and TNF-a between patients with ischemic heart failure, dilated cardiomyopathy, CAD and healthy controls. Methods: The population consisted of 20 patients with dilated cardiomyopathy, 48 patients with ischemic cardiomyopathy, 26 patients with CAD and normal left ventricle function and 14 healthy controls. Forearm blood flow was measured using venous occlusion strain gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to nitrate were considered as indexes of endothelium-dependent and endothelium-independent dilation, respectively. Results: Levels of IL-6 were significantly higher in ischemic cardiomyopathy compared to CAD patients (P < 0.05) or controls (P < 0.05) and in patients with dilated cardiomyopathy compared to controls (P < 0.05). TNF-alpha levels were significantly higher in both groups with ischemic or dilated cardiomyopathy compared to CAD (P < 0.05) or controls (P < 0.05). RH% was significantly lower in ischemic and dilated cardiomyopatby compared to CAD (P < 0.05) or controls (P < 0.001) and higher in dilated than ischemic cardiomyopathy (P < 0.05). Conclusions: Impaired endothelial function and increased inflammatory process were found in both types of heart failure. A greater endothelial dysfunction was observed in patients with ischemic heart failure compared to those with dilated cardiomyopathy, implying that the underlying atherosclerosis may participate in this process. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

The combined effects of smoking and hypercholesterolemia on the inflammatory process, the thrombosis/fibrinolysis system, and forearm hyperemic response were investigated. It was shown that smokers with hypercholesterolemia (n = 25) had a reduced and delayed forearm hyperemic response compared with healthy smokers (n = 24), patients with hypercholesterolemia (n 26), and healthy controls (n = 75; p < 0.01 for all). This phenomenon was associated with a respective increase in the inflammatory process and changes in the thrombosis/fibrinolysis system. (C) 2004 by Excerpta Medica, Inc.

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.

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.

Objective: To examine the effects of L-arginine on basal coronary tone and flow mediated dilatation induced by atrial pacing in patients with coronary artery disease and stable angina. Design: Atrial pacing was performed during intracoronary infusions of normal saline and L-arginine (150 mumol/min) in 8 patients with coronary artery disease and stable angina. The luminal diameter of epicardial coronary arteries was assessed by quantitative angiography. Results: L-Arginine administration significantly increased the diameter of all the coronary segments and stenoses. During atrial pacing with saline infusion, luminal diameter of the proximal, distal, and stenosis reference segments increased significantly (p < 0.01 versus saline) but stenosis diameter did not change. L-Arginine administration did not change the magnitude (NS) of atrial pacing induced dilatation in proximal and distal segments and in coronary stenoses and their reference segments. Conclusions: Non-stenotic segments of diseased coronary arteries dilate in response to atrial pacing but stenoses do not. L-Arginine dilates coronary segments and stenoses but does not increase the magnitude of the response to atrial pacing in proximal and distal segments and in coronary stenoses and their reference segments. These findings provide evidence that the shear stress responsive mechanism is absent at stenoses but present in non-stenotic segments of diseased coronary arteries. They also indicate a relative deficiency of L-arginine, except in the shear response mechanism.

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-I), 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 400IU/day (group B), vitamin C 2g/day plus vitamin E 800IU/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

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 lb (IL- lb) and 6 (IL-6), vascular cell adhesion molecule-1 (VCAM- 1), intercellular adhesion molecule-] (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 Q 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- I b, IL-6, sVCAM- I and sICAM- I 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-lb, 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. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

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 anti hypertensive 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.

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

Objective-To examine the effects of exogenous L- and D-arginine on coronary stenosis vasomotion in relation to stenosis morphology. Design-Intracoronary infusions of normal saline, L- and D-arginine (50 and 150 pmol/min), and glyceryl trinitrate (250 mug bolus) were given in 24 patients with coronary artery disease and stable angina. Coronary stenoses were classified as smooth or complex (irregular borders). The diameter of the coronary stenoses and their adjacent reference segments was measured by computed quantitative angiography. Results-During L-arginine infusion a larger proportion of complex stenoses than smooth stenoses dilated by greater than or equal to 10% (p < 0.01), and the magnitude of dilatation was greater at the site of complex stenoses (p < 0.05). Irrespective of the type of morphology there was a positive correlation (p < 0.01) between the severity of stenoses and the magnitude of vasodilatation to L-arginine. The response to glyceryl trinitrate was similar in the two groups. No significant change was found in either group in response to D-arginine. Conclusions-In patients with coronary artery disease, coronary stenoses-particularly those of complex morphology-dilate in response to the administration of L-arginine but not D-arginine. This finding is consistent with partial deficiency of the substrate for nitric oxide synthesis, L-arginine, at the site of complex stenoses.

L-Arginine is the substrate for nitric oxide production. Endothelium dysfunction could be attributed to L-arginine deficiency or the presence of L-arginine endogenous inhibitors. This hypothesis leads to the assumption that provision of L-arginine could be the key for endothelial function improvement. Many studies have proven that L-arginine has a beneficial effect on endothelium dependent vasoreactivity, as well as on the interaction between vascular wall, platelets and leucocytes. Therefore, individuals with risk factors for atherosclerosis and patients with coronary artery disease or heart failure, could benefit from therapy with L-arginine. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Percutaneous coronary transluminal angioplasty (PTCA) may release inflammatory mediators such as chemokines. Monocyte chemoattractant protein-1 (MCP-1) and eotaxin (EOX) are monocyte- and eosinophil-specific chemokines involved in the inflammation and pathogenesis of coronary atherosclerosis. A total of 28 patients undergoing elective PTCA, 20 coronary artery disease (CAD) patients undergoing coronary angiography and 28 healthy controls were studied. In PTCA patients before the procedure, MCP-1 plasma levels (441 +/- 64 pg/ml) were similar to those of CAD patients (430 +/- 24 pg/ml), and significantly higher compared with controls (145 +/-7 pg/ml, P

Objective-To assess the relation between coronary vasomotor effects of NG-monomethyl-L arginine (LNMMA) administration and coronary stenosis morphology, length, and severity in patients with stable angina. Design-In 28 patients (24 male, four female) with coronary artery disease and chronic stable angina, intracoronary normal saline and 4 mu mol/min LNMMA were infused for four minutes each, followed by an intracoronary bolus of 250 mug glyceryl trinitrate. Coronary stenoses were classified as concentric (smooth), eccentric (smooth), or complicated (irregular). The diameters of these stenoses and their adjacent reference proximal segments were measured by quantitative angiography. Results-During LNMMA infusion a significantly larger proportion of complicated stenoses than concentric and eccentric stenoses constricted by greater than or equal to 5% (p < 0.01) and the magnitude of vasoconstriction was greater in complicated than in concentric and eccentric stenoses (p < 0.05). For complicated stenoses the magnitude of constriction (in mm) with reference to normal saline was greater than that of the concentric and eccentric stenoses (p < 0.05), whereas concentric and eccentric stenoses constricted similarly. Irrespective of the type of morphology, there was a correlation (p < 0.05) between both the severity and the length of stenoses and the magnitude of vasoconstriction to LNMMA. A similar proportion of concentric, eccentric, and complicated stenoses showed greater than or equal to 5% increase in diameter with glyceryl trinitrate, and the magnitude of the response was similar in the three groups. Conclusions-In patients with coronary artery disease, the response to LNMMA is greater when stenosis morphology is complex, indicating greater nitric oxide activity. This provides further evidence that plaques with complex morphology are in an active state.

Nitric oxide is formed from the N-guanido terminal of the amino acid L-arginine and from molecular oxygen by nitric oxide synthase enzymes. L-arginine administration improves the coronary blood flow response to acetylcholine in patients with normal coronary arteries and hypercholesterolemia, reverses the defective endothelium-dependent vasodilation associated with an elevated plasma low-density lipoprotein level or hypercholesterolemia, dilates coronary epicardial arteries and stenoses, enhances nitric oxide generation, and inhibits lesion formation after balloon angioplasty. Stimulation of endogenous nitric oxide production could inhibit atherogenesis, and therefore may be of benefit in patients with risk factors for atherosclerosis. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

Objective-To assess the effects of substance P administration alone and in combination with L- and D-arginine in patients with normal angiograms and in patients with coronary artery disease. Design-Intracoronary infusions of (a) normal saline, (b) the receptor mediated nitric oxide stimulant substance P (5.6 and 27.8 pmol/min) before and after L- or D-arginine (50 and 150 pmol/min), and (c) glyceryl trinitrate (250 mu g bolus) were given to 17 patients with coronary artery disease and stable angina, and to six patients with normal angiograms. The diameter of angiographically normal proximal and distal segments and coronary stenoses were measured by computerised quantitative angiography. Results-L-arginine administration was associated with significant dilatation of stenoses (p < 0.01) of proximal segments of both “normal” (p < 0.05) and diseased (p < 0.01) arteries, and of distal segments of diseased arteries (p < 0.01). No significant changes were associated with D-arginine administration. Dose dependent dilatation of all segments including stenoses, was observed with substance P both before and after L-arginine infusion (p < 0.01). The magnitude of dilatation of stenoses and all segments of both “normal” and diseased coronaries was greater after L-arginine (p < 0.05) but not D-arginine and substance P infusion, than it was after saline and substance P infusion. Administration of D- or L-arginine did not change the magnitude of substance P induced dilatation. Conclusions-Diseased and “normal” coronary arteries dilated in response to substance P and L-arginine but were unaffected by D-arginine infusion. The magnitude of the response to substance P was not increased by L-arginine administration, indicating that it is not critically dependent on the availability of substrate for nitric oxide synthase.

Objective-To examine the effects of substance P (endothelium dependent vasodilator) and glyceryl trinitrate (endothelium independent vasodilator) on epicardial coronary arteries in patients with normal coronary angiograms and patients with coronary artery disease. Design-Intracoronary infusions of normal saline, the receptor mediated nitric oxide stimulant substance P (5.6 and 27.8 pmol/min each for five minutes), and glyceryl trinitrate (250 mu g bolus) were given in 24 patients with coronary artery disease and stable angina, and in nine patients with normal angiograms. The diameter of proximal and distal coronary segments was measured by computerised quantitative angiography Results-Proximal segments of patients with coronary artery disease dilated less than those of patients with normal angiograms in response to 27.8 pmol/min substance P (mean (SEM): 7.9 (1.3)% upsilon 15 (2.3)% respectively, p < 0.01). The proximal segments of diseased arteries also dilated less than those of “normal)) arteries in response to glyceryl trinitrate (10.2 (1.6)% upsilon 18.4 (2.9)%, respectively, p < 0.01). The responses of distal segments to substance P and glyceryl trinitrate were similar in the two patient groups. There were correlations tall p < 0.001) between the coronary diameter after substance P and after glyceryl trinitrate in normal proximal segments (r = 0.94) and normal distal segments (r = 0.64), in diseased proximal segments (r = 0.95) and diseased distal segments (r=0.89), and for coronary stenoses (r = 0.93). Conclusions-Proximal segments of patients with coronary disease dilated less than the proximal segments of ((normal)) patients in response to substance P and glyceryl trinitrate. The response to substance P is substantial and closely correlated with the response to glyceryl trinitrate in both (’normal)) patients and those with coronary disease. This suggests that although the probmal segments of diseased coronary arteries have a reduced capacity to dilate in response to direct stimulation of smooth muscle cell relaxation, they retain much of their endothelium dependent vasodilator function.