Contribution of Interleukin-6 system genes polymorphisms to the development of coronary atherosclerosis.

Coronary artery disease (CAD) continues to be a main cause of high cardiovascular morbidity and mortality and its prevalence is expected to increase as the population ages, so its prevention is a key public health policy goal. The risk of developing atherosclerosis is related to a complex interaction of genetic, environmental and lifestyle factors. Significant progress has been made in understanding the genetic architecture of this disease in the last decade.

[Possibilities of clinical use of ezetimibe Otrio (JSC "AKRIKHIN", Russia) in patients with high and very high cardiovascular risk who have not reached the target values of lipid metabolism. Conclusion of the Board of experts].

This Conclusion of the Board of experts is devoted to the analysis of the evidence base, the position in modern clinical guidelines, the efficacy and safety analysis as well as the options of combined therapy with statins and ezetimibe (Otrio, JSC "AKRIKHIN") in various categories of patients in routine clinical practice in theRussian Federation. Cardiovascular diseases (CVD) continue to lead in the structure of morbidity and mortality inRussia. Hypercholesterolemia is one of the main modifiable risk factors for CVD.

The association of PLA2G2A single nucleotide polymorphisms with type IIa secretory phospholipase A2 level but not its activity in patients with stable coronary heart disease.

Background: Single nucleotide polymorphisms (SNPs) of the secretory phospholipase A2 type IIa (sPLA-IIa) gene (PLA2G2A) affect sPLA2-IIa level and activity in patients with diabetes mellitus, acute coronary syndrome or recent cardiovascular surgical interventions. Our study examined the effects of PLA2G2A SNPs on sPLA2-IIa levels and activity in patients with stable CHD.

Methods And Results: The study included a total of 396 patients (30% women).

A cytofluorometric study of membrane rafts in human monocyte subsets in atherosclerosis.

The peripheral blood monocytes of atherosclerotic patients are pre-activated and have some of the features of tissue macrophages. Their adhesion to the endothelium is 1.5 times higher than that of monocytes from healthy subjects, and they express a number of receptors and antigens typical of tissue macrophages.

[Comparison of the efficiency of transluminal balloon angioplasty using EucaTAX and Cypher stents in patients with stable coronary heart disease].

Objective: To compare the long-term results of transluminal balloon coronary angioplasty in patients after implantation of drug-eluting coronary artery stents with permanent or biosoluble polymer coatings.

Material And Methods: This was a prospective, comparative, single-center trial. It enrolled patients having at least 70% stenosis who had undergone intracoronary Cypher (SES) or EucaTAX (EUPES) stent implantation.

Two-year follow-up of percutaneous coronary intervention using EucaTax or Cypher.

Background: The EucaTax stent (EUPES) is a coronary stent with biodegradable polymer and camouflage coating that has been developed to promote the complete elution of drugs and decrease the risk of late complications. The aim of this study was to evaluate the efficacy and safety of the double-coated EUPES in patients with stable angina versus sirolimus-eluting stent CYPHER (SES) with permanent polymer coating.

Methods And Materials: The study included consecutive patient with at least 70% de novo coronary lesions in one or two native coronary arteries and who had undergone the coronary stenting using either EUPES or SES.

Association between polymorphisms of eNOS and GPx-1 genes, activity of free-radical processes and in-stent restenosis.

Our aim was to examine correlations between polymorphisms in five antioxidant enzymes genes, activity of free-radical processes, and the risk of restenosis after coronary artery stenting with bare metal stents (BMS). A total of 101 male patients who underwent intracoronary stenting using BMS and coronary angiography follow-up of 6 months were enrolled in: group with in-stent restenosis (n = 44) and without restenosis (n = 57). The content of lipoperoxides and malondialdehyde (MDA) in Low-density lipoprotein (LDL), activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) in erythrocytes, and genotypes polymorphisms of the CAT gene (-262C/T), paraoxonase-1 (PON-1) gene (163T/A and 575A/G), endothelial nitric oxide synthase (eNOS) gene (298G/T (rs#1799983) and -786T/C), GPx-1 gene (599C/T (rs#1050450)), and glutathione-S-transferase (GSTP) gene (313A/G) were determined.

Pro198Leu polymorphism of GPx-1 gene and activity of erythrocytic glutathione peroxidase and lipid peroxidation products.

We studied the relationship between the GPx-1 gene Pro198Leu polymorphism genotype and activity of free-radical processes. In patients with documented CHD, the content of lipoperoxides and MDA in LDL, activity of glutathione peroxidase in erythrocytes, and genotype of GPx-1 gene Pro198Leu polymorphism were determined. In carriers of the minor allele, activity of glutathione peroxidase in erythrocytes was lower by 17% than in wild allele homozygotes, while the content of lipoperoxides and MDA in LDL was higher by 74 and 27%, respectively.

[Antioxidant status and restenosis after stenting of coronary arteries].

Aim: To investigate possibility of effect of antioxidant status on severity of restenosis of coronary arteries after transluminal coronary angioplasty with stenting.

Material And Methods: Men with ischemic heart disease and coronary angiography performed in 6 months after coronary artery stenting with bare stents were included in this study. Coronary angiograms were subjected to quantitative computer analysis.

Relationship between free-radical lipid oxidation and efficiency of coronary angioplasty in coronary patients.

Low-dose (250 mg daily) oral probucol produces a significant antioxidant effect in coronary patients: increases activity of glutathione peroxidase (enzyme utilizing lipoperoxides) and reduces the content of free-radical oxidation products in the blood. Probucol therapy for 7 days before and for 6 months after coronary angioplasty significantly reduces the severity of coronary artery stenosis.

[Effect of atorvastatin therapy on the level of secretory phospholipase A2 group IIA and on the modification of low density lipoproteins in patients with ischemic heart disease].

We studied effect of atorvastatin on secretory phospholipase A2 group IIA (sPLA2-IIA) in blood serum of patients with ischemic heart disease (IHD), lipid composition of low density lipoproteins (LDL) and process of modification of LDL induced by sPLA2-IIA in 20 patients taking 20 mg/day of atorvastatin for 3 months. In patients with initially high level of sPLA2-IIA ( > 8 mcg/l) its concentration significantly decreased. Amount of total cholesterol, triglyceride, lecithin, and lysolecithin remained unchanged, however in equimolar relations there occurred decrease of amount of total cholesterol and increase of cholesterol esters.

Effect of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors and antioxidant vitamins on free radical lipid oxidation in rat liver.

We studied the effects of two inhibitors of beta-hydroxy-beta-methylglutaryl coenzyme A reductase, simvastatin and lovastatin, on the lag phase of ascorbate-dependent lipid oxidation in rat liver. Oxidizability of liver biological membranes significantly increased in intact animals and rats with induced hypercholesterolemia after peroral administration of these statins. The lag phase of ascorbate-dependent lipid oxidation in liver biomembranes decreased by 2.

Effect of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor atorvastatin on contractility of the isolated rat heart under normal conditions and during oxidative stress.

Long-term administration of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor atorvastatin to rats was accompanied by an increase in the relative weight of the heart and decrease in the rate of pressure development in the isovolumic heart. During oxidative stress induced by addition of 100 microM H2O2 to the perfusate, the decrease in contractile function was more pronounced that in the control. Our results indicate that administration of atorvastatin is accompanied by a decrease in myocardial contractility, which becomes more pronounced under conditions of oxidative stress.

Effect of ubiquinone Q(10) and antioxidant vitamins on free radical oxidation of phospholipids in biological membranes of rat liver.

We studied the effects of 30-day peroral treatment with beta-carotene, a complex of antioxidant vitamins (vitamins C and E and provitamin A) and selenium, and solubilized ubiquinone Q(10) on the antioxidant potential in rat liver (ascorbate-dependent free radical oxidation of unsaturated membrane phospholipids). beta-Carotene irrespective of the administration route increased antioxidant potential of the liver by 2-3.5 times.

Oxidative stress in atherosclerosis and diabetes.

We measured the content of lipid peroxides in plasma LDL from patients with chronic CHD not accompanied by hypercholesterolemia; CHD and hypercholesterolemia; type 2 diabetes mellitus and decompensation of carbohydrate metabolism; and CHD, circulatory insufficiency, and type 2 diabetes mellitus (without hypercholesterolemia). The content of lipid peroxides in LDL isolated from blood plasma by differential ultracentrifugation in a density gradient was estimated by a highly specific method with modifications (reagent Fe(2+) xylene orange and triphenylphosphine as a reducing agent for organic peroxides). The content of lipid peroxides in LDL from patients was much higher than in controls (patients without coronary heart disease and diabetes).

Low daily dose of antioxidant probucol decreases incidence and severity of restenosis after transluminal coronary balloon angioplasty.

Antioxidant probucol in both high (1000 mg) and low (250 mg) daily doses effectively reduced manifestations of oxidative stress in patients with atherosclerosis (assessed by in vivo accumulation of lipoperoxides in atherogenic LDL). When probucol was administered in a dose of 250 mg/day for 7-10 days before transluminal balloon coronary angioplasty and then for 6 months after surgery, the incidence of restenosis decreased to 25% compared to 45% in the control (without probucol therapy). In the group of operated patients receiving probucol (250 mg/day for 6 months) the minimal artery lumen was significantly higher, and the degree of artery occlusion significantly lower than in the control group not treated with probucol.

Changes in antioxidant status of myocardium during oxidative stress under the influence of coenzyme Q10.

Changes in myocardium were studied during oxidative stress induced by infusion of hydrogen peroxide in the coronary vessels of isolated rat heart. Moderate concentrations of H2O2 increased the heart rate but decreased the contractile force, whereas higher concentrations of H2O2 decreased both parameters and increased the end diastolic pressure. The effect of H2O2 was stable, cumulative, and was associated with disturbance in respiration of mitochondria, increased production of ROS in them, and decrease in activities of antioxidant enzymes in the myocardium.

Antioxidants decreases the intensification of low density lipoprotein in vivo peroxidation during therapy with statins.

The oxidative modification of low density lipoprotein (LDL) is thought to play an important role in atherogenesis. Drugs of beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) family are usually used as a very effective lipid-lowering preparations but they simultaneously block biosynthesis of both cholesterol and ubiquinone Q10 (coenzyme Q), which is an intermediate electron carrier in the mitochondrial respiratory chain. It is known that reduced form of ubiquinone Q10 acts in the human LDL as very effective natural antioxidant.

[Serum level of secretory phospholipase A2 (sPLA2) as a predictor of restenosis after coronary angioplasty].

Aim: To elucidate whether secretory phospholipase A2 (sPLA2) level in the blood and catalytic activity are significant predictors of restenosis after coronary angioplasty (CAP).

Material And Methods: Samples of venous blood were obtained from 24 patients before CAP and 1, 3, 6 days and 6 months after it. sPLA2 was measured with enzyme immunoassay, catalytic activity--using aqueous emulsion of 14C-labelled phosphatidylcholine.