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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 [...]

Aims Inhibition of nitric oxide synthesis causes a decrease in the basal diameter of normal distal epicardal coronary arteries in normal subjects. The effects of inhibition of nitric oxide in atheromatous coronary arteries is unknown. This study assessed the effects of the inhibition of nitric oxide synthesis in epicardial coronary arteries in patients with coronary artery disease. Methods and results The effects of an intracoronary infusion of NG-monomethyl-L-arginine (LNMMA, an inhibitor of nitric oxide synthesis), were studied in 13 patients with chronic stable angina and coronary artery disease. The diameter of angiographically normal proximal and distal segments and coronary stenoses was measured by quantitative angiography. In response to an LNMMA infusion of 16 μmol min−1 for 4 min there was a significant reduction (P<0·01) in the luminal diameter of the distal segments of diseased arteries (from 1·32 ± 0·07 to 1·17 ± 0·06 mm) and at the site of stenosis (from 1·15 ± 0·22 to 1·06 ± 0·20 mm), but no change (P=NS) in the luminal diameter of the proximal segments (from 3·16 ± 0·12 to 3·08 ± 0·14 mm) of diseased arteries. Conclusions The average effect of inhibition of basal nitric oxide synthesis in epicardial coronary arteries in patients with stable angina and coronary artery disease was only distal constriction. Coronary stenoses constricted at the highest LNMMA concentration. [ABSTRACT FROM PUBLISHER]

We studied 12 patients (eight females and four males), ages 30–46 years, with echocardiographically documented mitral valve prolapse and clinical suspicion of coronary artery disease, based on a history of chest pain (five patients), angina-like pain (three patients), a positive exercise stress electrocardiogram (12 patients) and a focally positive thallium-201 stress perfusion scan (three patients), who were referred for cardiac catheterization and found to have normal coronary arteries. Ten patients without evidence of heart disease served as controls. In all mitral valve prolapse patients, coronary flow velocity reserve was determined successively in the left anterior descending, left circumflex and right coronary arteries as the ratio of the maximun (after intracoronary papaverine) to the resting mean coronary flow velocity. Coronary flow reserve values were fairly similar in the mitral valve prolapse and control patients; all 12 mitral valve prolapse patients had normal coronary flow reserve (≥3.5) in all three coronary arteries with no significant differences among the arteries tested Mean values ± 1 standard deviation of the coronary flow reserve (mitral valve prolapse vs control patients) were 4.7 ± 0.5 vs 4.6 ± 0.6 for the left anterior descending, 4.6 ± 0.4 vs 4.6 ± 0.3 for the left circumflex and 4. ± 0.4 vs 4.4 ± 0.5 for the right coronary artery (all P=non-significant). The subsets of mitral valve prolapse patients with different clinical ‘ischaemic’ manifestations were similar in terms of the calculated coronary flow reserve in all three major epicardial coronary arteries. In conclusion, this study demonstrated that an inadequate regional coronary flow reserve does not account for the clinical manifestations of myocardial ischaemia and positive exercise tests in patients with mitral valve prolapse and normal coronary arteries. [ABSTRACT FROM PUBLISHER]

Previous studies have demonstrated the development of vasoconstriction immediately after percutanous coronary angioplasty (PTCA), distal to the dilated stenosis, presumably resulting from endothelial injury. We have investigated the role of 5-HT receptors in mediating vasomotor changes in proximal and distal coronary segments and coronary stenoses, immediately after successful PTCA in patients with chronic stable angina. We compared the effects of the intracoronary infusion of 1 mg ketanserin (5-HT receptor antagonist) on proximal and distal coronary arterial segments immediately after PTCA in both vessels subjected to PTCA and control vessels. Coronary diameters, before and after angioplasty and after ketanserin administration, of proximal and distal segments and coronary stenoses were measured by computerized quantitative coronary angiography (CAAS system) in 12 patients (10 male, two female; mean age 54 ±6 years) with stable angina subjected to PTCA. After coronary angioplasty, vasoconstriction was observed in the segment distal to the dilated stenosis but not in the distal segments of control vessels ( − 0.12 ± 0.04 and − 0.02 ± 0.02 mm respectively, P<0.05). After ketanserin infusion significant dilatation was found in the distal segments of both PTCA vessels and control vessels, but the dilatation was greater in the PTCA vessels (P<0.05). No significant changes were found in the proximal segments of either PTCA or control vessels, or at the PTCA site. In conclusion, the vasoconstriction distal to the site of PTCA is mediated, at least in part, via 5-HT receptors. [ABSTRACT FROM PUBLISHER]

An abstract of the article "Short-term treatment with rosuvastatin reduces plasma levels of myeloperoxidase in patients with heart failure," by I. Andreou and colleagues is presented.

An abstract of the study "Effects of the Ca2+-Sensitizer Levosimendan Continuous Infusion on Inflammatory Process in Patients With Advanced Congestive Heart Failure," by A. Trikas and colleagues is presented.

An abstract of the article "Rosuvastatin positively influences extracellular matrix remodelling in patients with heart failure," by I. Andreou and colleagues is presented.

An abstract of the article "Dinstinct pro-inflammatory cytokines regulate matrix metalloproteinase-2 and 9 levels in congestive heart failure," by I. Andreou and colleagues is presented.

An abstract of the article "Allopurinol increases endothelial progenitor cell number in patients with heart failure," by I. Andreou and colleagues is presented.

An abstract of the study "Cytokines and Oxidative Stress Do Not Regulate Asymmetrical Dimethylarginine (ADMA) Levels in Congestive Heart Failure," by Y. Andreou and colleagues is presented.

The article presents the abstract of the study "Anti-Depressive Medication Decreases Tumor Necrosis Factor Alpha and C-Reactive Protein in Patients with Congestive Heart Failure," by D. Tousoulis and colleagues.

The article presents an abstract of the study "Atorvastatin Exerts Global Anti-Inflammatory and Antithrombotic Effects in Patients with Congestive Heart Failure," by C. Antoniades and colleagues.

An abstract of the study "Beta Blockers Improve Long-Term Survival in Patients With End-Stage Heart Failure and Depression, Only When Combined With Selective Serotonin Reuptake Inhibitors," by A. Trikas and colleagues is presented.

An abstract of the study "The type of heart failure and its effects on endothelial function and inflammatory process: differences between ischemic and dilated heart failure," by C. Antoniades and colleagues, is presented.

We examined the impact of serum cholesterol and cigarette smoking on the coronary vasomotor effects of L-arginine in patients with atherosclerotic coronary artery disease. The dilation of proximal and distal segments in response to low-dose L-arginine was greater in patients with a serum cholesterol level < or =200 mg/dl than in patients with a level >200 mg/dl, whereas the response was the same in smokers and nonsmokers. [ABSTRACT FROM AUTHOR]

We assessed the effects of intracoronary administration of substance P, LNMMA, L-arginine, and nitroglycerin in patients with normal coronary angiograms and in patients with coronary artery disease. LNMMA constricted (p <0.01) and both substance P and nitroglycerin dilated normal and diseased proximal and distal segments and stenoses (p <0.01). L-Arginine reversed the effect of LNMMA in all segments and caused greater dilation of the diseased arteries, including stenoses (p <0.05), indicating that there is a relative deficiency of L-arginine in diseased coronary arteries. [ABSTRACT FROM AUTHOR]

We measured the changes of plasma von Willebrand factor antigen and fibrinogen levels in patients with acute myocardial infarction treated with recombinant tissue plasminogen activator and patients not given fibrinolytic drugs. The von Willebrand factor levels are greater in patients with Q-wave than in patients with non-Q-wave myocardial infarction and are independent of thrombolytic treatment. Fibrinogen levels are depressed by thrombolytic treatment but are unrelated to the presence or absence of Q waves. [ABSTRACT FROM AUTHOR]

Introduction: Early statin treatment has beneficial effects on the prognosis after acute coronary syndromes. We investigated the impact of prior statin treatment on the outcome of patients without a prior history of coronary artery disease (CAD) who presented with ST-elevation myocardial infarction (STEMI) and were treated with thrombolysis., Methods: The study enrolled 1032 consecutive patients who satisfied the above criteria. They were categorized into two groups, based on their prior statin treatment for at least 3 months before admission: the statin pretreatment group (n=124) and the statin-naïve group (n=908). All patients received high-dose statins during hospitalization and were prescribed statins after discharge. The primary outcome was the incidence of successful thrombolysis, as expressed by the percentage of patients with 50% ST-segment resolution and complete retrosternal pain resolution at 90 minutes. Secondary outcomes included reduction in high-sensitivity C-reactive protein (hs-CRP) and CK-MB levels, and in-hospital, short- and long-term cardiovascular mortality., Results: ST-segment resolution 50% was observed in 63.7% of the statin-pretreatment group and in 49.1% of statin-naïve patients (p<0.01). Statin pretreatment was associated with lower hs-CRP and peak CK-MB levels (p<0.001). The statin-pretreatment group had lower 30-day mortality (5.6% vs. 12.3%, p<0.05), whereas no significant differences were detected in in-hospital or 3-year mortality., Conclusions: Prior statin treatment in patients without a history of CAD who present with STEMI is associated with successful thrombolysis, decreased systemic inflammation, a lesser degree of myocardial damage, and a possible reduction in short-term mortality.

Background: Adiponectin is an adipokine with an important role in cardiovascular system conferring anti-inflammatory and anti-atherogenic effects. Two common single nucleotide polymorphisms (SNP) on adiponectin gene, rs2241766 and rs1501299, have been associated with insulin resistance and diabetes mellitus risk however their effects on cardiovascular risk remain unclear. We examined the impact of rs2241766 and rs1501299 on circulating adiponectin levels, endothelial function and cardiovascular disease risk., Methods: We recruited in total 594 subjects; 462 patients with angiographically confirmed coronary artery disease (CAD) and 132 controls matched for age and gender. rs2241766 and rs1501299 were genotyped by polymerase chain reaction and restriction endonuclease digestion. Serum adiponectin levels were determined by enzyme-linked immunosorbent assay. Endothelial function was assessed by the flow mediated dilatation (FMD) of the brachial artery., Results: rs2241766 had no effects on circulating adiponectin levels or FMD. In subjects without CAD, carriers of the T/T alleles at rs1501299 had lower adiponectin levels (p=0.001) and impaired endothelial function (p<0.05). After multivariate adjustment none of the SNPs had any effect on CAD risk. However, carriers of the T allele at rs1501299 were at increased myocardial infarction (MI) risk, independently of classic risk factors (OR=2.558 [95%CI=1.587-4.123], p=0.0001). The number of T alleles in both SNPs was strongly associated with MI history (p=0.0001)., Conclusions: rs1501299 polymorphism of adiponectin gene affects circulating adiponectin levels and endothelial function in subjects without CAD. Presence of the T variant at rs1501299 on adiponectin gene is independently associated with increased myocardial infarction risk., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Endothelial dysfunction represents an imbalance between vasodilatory and vasoconstrictory molecules secreted by endothelium. Oxidative stress is a major factor leading to endothelial dysfunction with significant prognostic implications for cardiovascular events. The generation of reactive oxygen species is strongly related to various oxidase enzymes such as xanthine oxidase, uncoupled endothelial nitric oxide synthase, cyclooxygenase, glucose oxidase, lipooxygenase, nicotinamide-adenine dinucleotide phosphate oxidase and to mitochondrial electron transport mechanisms. Several pharmaceutical agents exert effects beyond their principal role, such as anti-inflammatory and antioxidant, while the reports on antioxidant vitamins remain controversial especially those based on large scale studies. Moreover, there are studies on other agents already patented, but these are not well evaluated. Recently, there is growing interest in the role of dietary flavonoids and their potential to improve endothelial function by modifying oxidative stress status. Flavonoids are important components of 'functional foods', with beneficial effects on cardiovascular health, mainly due to their antioxidant activity. However, the vascular-protective role of flavonoids and especially their antioxidant properties are still under investigation.

The increasing prevalence of coronary artery disease (CAD) as well as its&#39; monitoring remain crucial problems and fields of long debate. Thus, several circulating biomarkers have been found during the last decade and examined in terms of their potential to assist in the prognosis of CAD. Of great interest, are small non-coding RNAs (microRNAs or miRNAS or miRs), due to their association with many aspects of CAD. microRNAs circulate in the bloodstream, while they exist in tissues and affect plaque initiation and progression. In addition, they have been found to contribute to the pathophysiology of CAD and to the CAD-related manifestations such as myocardial infarction, heart failure and cardiac arrhythmias. Therefore, evaluating the role of these molecules may be of great importance in the understanding of atherogenesis providing new evidence for diagnosis and prognosis of CAD.

Background: The elastic properties of the ascending aorta were studied before and 1 week after transcatheter aortic valve implantation (TAVI). Previous studies have shown that the distensibility of the ascending aorta was decreased in the early post-operative period after aortic valve replacement. Aortic stiffness is a major moderator of arterio-ventricular coupling and an independent predictor of cardiovascular risk and mortality. We evaluated the effect of TAVI on the elastic properties of the ascending aorta in the early post-operative period., Methods: Aortic distensibility (AD) and Aortic Stiffness Index (ASI) were evaluated using echocardiographic techniques and brachial artery pressure obtained by sphygmomanometry 2-3 days before and 7-8 days after TAVI., Results: A total of 30 patients (14 males) were studied with a mean age of 79.9 ± 4.7 years and aortic valve area before TAVI of 0.61 ± 0.16 cm(2). Mean arterial pressure decreased significantly after TAVI (from 89.6 ± 8.9 mmHg to 83.3 ± 10.9 mmHg, p = 0.004). AD did not change significantly after TAVI (pre: 1.89 ± 1.11 cm(2)/(dynes × 10(6)), post: 2.05 ± 1.50 cm(2)/(dynes × 10(6)); p = 0.813). ASI also remained unchanged (pre: 11.4 ± 6.5, post: 15.6 ± 14.9; p = 0.349)., Conclusions: The elastic properties of the ascending aorta did not change significantly in the early post-procedural period after TAVI. This may in part be attributable to the less invasive procedure (compared to aortic valve replacement) which has no effect on vasa vasorum flow.

Nitric oxide (NO) is a soluble gas continuously synthesized from the amino acid L-arginine in endothelial cells by the constitutive calcium-calmodulin-dependent enzyme nitric oxide synthase (NOS). 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 (including statins, angiotensin converting enzyme inhibitors/angiotensin receptors blockers, insulin sensitizers, antioxidant compounds) are now available, targeting both the synthesis and oxidative inactivation of NO in human vasculature, reversing in that way endothelial dysfunction which is enhanced by the release of nitric oxide from the endothelium.

The vascular endothelium is a monolayer of cells between the vessel lumen and the vascular smooth muscle cells. Nitric oxide (NO) is a soluble gas continuously synthesized from the amino acid L-arginine in endothelial cells by the constitutive calcium-calmodulin-dependent enzyme nitric oxide synthase (NOS). This substance has a wide range of biological properties that maintain vascular homeostasis, including modulation of vascular dilator tone, regulation of local cell growth, and protection of the vessel from injurious consequences of platelets and cells circulating in blood, playing in this way a crucial role in the normal endothelial function. A growing list of conditions, including those commonly associated as risk factors for atherosclerosis such as hypertension, hypercholesterolemia, smoking, diabetes mellitus and heart failure are associated with diminished release of nitric oxide into the arterial wall either because of impaired synthesis or excessive oxidative degradation. The decreased production of NO in these pathological states causes serious problems in endothelial equilibrium and that is the reason why numerous therapies have been investigated to assess the possibility of reversing endothelial dysfunction by enhancing the release of nitric oxide from the endothelium. In the present review we will discuss the important role of nitric oxide in physiological endothelium and we will pinpoint the significance of this molecule in pathological states altering the endothelial function.

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.

It is well established that matrix metalloproteinases (MMPs) contribute to the degradation of the extracellular matrix of coronary plaque and contribute to the thinning of the fibrous cap. As a result, the atheromatous plaque becomes unstable and prone to rupture with consequent clinical manifestations including acute coronary syndromes. Moreover, genetic polymorphisms of MMPs have been found to be associated with the concentration of circulating MMPs, and over the past decade, considerable efforts have been devoted to explore the relationships between MMPs polymorphisms and myocardial infarction risk among various populations. However, existing studies have yielded inconsistent results. Some observations have suggested that genetic variation that affects the expression of MMPs may contribute to the occurrence of myocardial infarction, whereas others reported no support for an association of MMPs polymorphisms with myocardial infarction susceptibility. Furthermore, the interpretation of these studies has been complicated by the use of different populations or different control sources. Therefore, further studies are required to evaluate the role of matrix metalloproteinases and especially the associated genetic polymorphisms in cardiovascular disease.

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.

Objective: Endothelial progenitor cells (EPCs) contribute to the maintenance of endothelial integrity and function. We investigated the effects of rosuvastatin and allopurinol on the number of EPCs in patients with heart failure and aimed to provide insight into the molecular inflammatory and oxidative mechanisms that could be responsible for the alterations in EPC levels after treatment., Methods: Sixty patients with systolic heart failure were randomized to receive rosuvastatin 10mg/d, allopurinol 300mg/d or placebo and followed up for 1 month. The number of CD34(+)/KDR(+) and CD34(+)/CD133(+)/KDR(+) EPCs in blood was evaluated by flow cytometry. Endothelial function was assessed by brachial artery flow-mediated dilation. Levels of markers of inflammation and oxidative stress were also determined., Results: Circulating EPCs were significantly increased after rosuvastatin treatment (from 230 (170-380) and 10 (8-24) to 390 (230-520) and 19 (8-33) cells/10(6) lymphomonocytes, respectively, p=0.004 and p=0.008), whereas they remained unchanged in the other groups. The increase in EPC levels was not associated with the changes in the levels of the measured inflammatory and oxidative markers., Conclusion: Short-term treatment with rosuvastatin, but not allopurinol, significantly increases the number of circulating EPCs in patients with heart failure providing further insights into its role in these individuals. The impact of rosuvastatin on EPCs is not mediated by changes in inflammatory and oxidative status., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Patients with chronic heart failure (HF) are characterized by alterations in matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) levels. However, the impact of hypolipidemic and antioxidant treatment in MMPs and TIMPs is unknown. In the present study, we sought to compare the effects of statins and xanthine oxidase inhibitors on circulating levels of MMPs and TIMPs in patients with chronic HF., Methods: Forty-two clinically stable patients with mild to moderate HF were randomized to receive rosuvastatin 10 mg or allopurinol 300 mg daily and followed up for 1 month. Serum levels of MMP-2, -9, TIMP-1, and -2 were measured before and after treatment., Results: Levels of MMP-2 and -9 were significantly decreased in the rosuvastatin group (from 251±52 ng/ml and 400±206 ng/ml to 215±47 ng/ml and 309±166 ng/ml, p<0.001 and p<0.05 respectively), but not in the allopurinol group. In the rosuvastatin group, TIMP-2 levels were significantly increased (from 85±17 ng/ml to 93±16 ng/ml, p<0.05), while TIMP-1 remained unchanged. In the allopurinol group, no significant changes were observed regarding the levels of TIMPs., Conclusions: Short-term rosuvastatin but not allopurinol administration decreases MMP-2 and -9 and increases TIMP-2 levels., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)