Marlena Broncel

Damage to the structure of erythrocyte plasma membranes in patients with type-2 hypercholesterolemia

BACKGROUND Hypercholesterolemia may decrease the deformability of red blood cells which impairs their hemorheological behavior and promotes atherosclerosis. The study involved 60 hypercholesterolemic patients and 30 healthy individuals as the control group. METHODS The membrane fluidity of erythrocytes was estimated by a spin-label method (5-doxylstearic acid (5-DSA)). The ratio of weakly to strongly (W/S) immobilized residues of erythrocyte membrane-bond maleimide-tempo spin label was studied in oxidative damage to membrane protein. Damage to erythrocyte proteins was also indicated by means of Na(+) K(+) ATPase activity. RESULTS The membranes of hyperlipidemia (hlp) patients contain larger concentrations of cholesterol 2.16+/-0.24 than do those of the normolipemic individuals 0.31+/-0.24 (P<0.001). The level of Na(+) K(+) ATPase in the erythrocyte membrane from the control group was higher 103.4+/-1.3 (nmolPi/(mgproteinsh)) than in the patient group 93.6+/-3.2 (nmolPi/(mgproteinsh)) (P<0.001). The order parameter S 5-DSA in the control group was 0.745+/-0.009 and in hlp patients was 0.755+/-0.009 (P<0.001). The W/S ratio in the control group amounted to 2.00+/-0.09 and in the hlp patient group was 2.50+/-0.11 (P<0.001). CONCLUSION Type-2 hypercholesterolemia causes changes in the structure and fluidity of erythrocyte plasma membranes since the excess of cholesterol affects the normal rheology of blood through its interaction with erythrocytes. It also impairs the function and structure of plasma membrane proteins.

Effect of polyphenols extracts from Brassica vegetables on erythrocyte membranes (in vitro study)

The aim of this work was to estimate the in vitro effects of polyphenol extracts from Brassica vegetables (Brussels sprouts and red cabbage) on erythrocyte membranes with normal and high concentration of cholesterol. To determine the effect of phenolic compounds we prospectively studied cholesterol concentration, lipid peroxidation, membrane fluidity and ATPase activity. Polyphenol extracts from Brassica vegetables resulted in statistically significant reductions in cholesterol concentrations in hypercholesterolemic erythrocytes. For control erythrocytes, no significant reduction of cholesterol levels was observed for both extracts. Decreases in lipid peroxidation intensity were observed after incubation of hypercholesterolemic erythrocytes with the extracts. No changes in membrane fluidity for both extracts were noted for normal and hypercholesterolemic erythrocytes. The activity of ATPase decreased after incubation of normal and hypercholesterolemic erythrocytes with extract from Brassica vegetables. Our results indicate that polyphenols from red cabbage and Brussels sprout may directly influence erythrocyte membrane properties.

Increased oxidative stress and decreased membrane fluidity in erythrocytes of CAD patients

One of many risk factors for cardiovascular disease appears to be oxidative stress. To estimate possible changes in redox balance, membrane fluidity, and cholesterol level in erythrocytes was collected erythrocytes from patients diagnosed with coronary artery disease (CAD). The study included 20 patients with previous myocardial infarction occurring more than 6 months prior to the time of screening with low-density lipoprotein cholesterol (LDL-C) > 70 mg/dL and 21 healthy controls. The following parameters were studied: catalase, glutathione peroxidase (GPx), superoxide dismutase (SOD), thiobarbituric acid reactive substrates (TBARS), sulfhydryl (SH) groups in membrane protein, total cholesterol level, and erythrocyte membrane fluidity. Our study showed an increase in the level of lipid peroxidation (13%) and total cholesterol (19%), and a decrease in membrane fluidity (14%) in the subsurface layers and in the deeper layers of erythrocyte membrane (7%) isolated from patients with CAD in comparison to healthy controls. A significant decrease in catalase (10%) and SOD (17%) activities were also observed. No changes in GPx activity or the level of SH groups were observed. Our study indicates that there are disorders in the antioxidant system as well as changes in the membrane structure of erythrocytes obtained from CAD patients.

The effect of melatonin on circadian blood pressure in patients with type 2 diabetes and essential hypertension

Introduction The aim of this study was to evaluate the effect of melatonin on blood pressure in patients with essential hypertension receiving medical treatment and with type 2 diabetes in good metabolic control. Material and methods The study lasted 8 weeks. Patients were equipped with a 24-hour ambulatory blood pressure monitor and took melatonin (3 mg a day in the evening) for 4 weeks. The patients were divided into four groups: group 1 (n = 32) including dippers, group 2 (n = 34) non-dippers treated with melatonin; and two control groups: group 3 (n = 28) including dippers and group 4 (n = 30) non-dippers treated without melatonin. After 4 weeks patients took melatonin for the next 4 weeks (5 mg a day). In each visit were analyzed: systolic, diastolic and mean blood pressure in both day and night time. Results We observed that 29.5% non-dippers (n = 10) treated with melatonin in a dose of 3 mg/day achieved features of dippers compared to control group (p < 0.05). Five mg of melatonin per day restored normal diurnal blood pressure rhythm in 32.4% non-dippers (n = 11, p < 0.05). In non-dippers treated with melatonin significant decreases of diastolic, systolic and mean night blood pressure values (p < 0.05) were observed. Conclusions More than 30% of non-dippers with type 2 diabetes treated with melatonin were restored to the normal circadian rhythm of blood pressure. The effect of melatonin in both doses (3 mg and 5 mg) was significant for non-dippers only and included nocturnal systolic, diastolic and mean arterial pressure.

Echocardiographic indices of left ventricular hypertrophy and diastolic function in hypertensive patients with preserved LVEF classified as dippers and non-dippers

Introduction Long-lasting arterial hypertension causes left ventricular hypertrophy (LVH) and impairs left ventricular diastolic function. Our aim was to compare echocardiographic parameters between hypertensive patients defined as dippers and non-dippers during ambulatory blood pressure (BP) monitoring. Material and methods We analysed 61 consecutive subjects with treated hypertension undergoing 24-h BP monitoring and transthoracic echocardiographic examination and included in the study patients with preserved left ventricular ejection fraction (EF ≥ 50%). Echocardiographic and arterial pressure parameters were compared between the group classified as dippers (n = 26, 57 ±13 years, 16 males) and non-dippers (n = 35, 60 ±12 years, 24 males) according to present or absent decrease of BP during the night > 10%. Echocardiographic data were compared between both groups and control subjects without hypertension. Results Dippers had lower average systolic, diastolic and mean arterial pressure during the night hours but did not differ according to the mean pressure calculated from a 24-hour period. All echocardiographic parameters were similar in dippers and non-dippers. All patients with arterial hypertension presented with larger dimension of both ventricles and left atrium, thicker left ventricular walls, higher LV mass and mass index and preserved EF and E/A ratio as compared with normotensive controls. Normal geometry, concentric remodelling and eccentric hypertrophy were similarly distributed in both groups. Concentric hypertrophy was more prevalent in non-dippers as compared to the dippers (71.4% vs. 38.5%, p < 0.043). Conclusions The concentric type of LVH is the prevalent pattern in non-dippers. Non-dipping blood pressure pattern may be responsible for the development of left ventricular concentric hypertrophy secondary to hypertension.

Comprehensive insight into immune regulatory mechanisms and vascular wall determinants of atherogenesis – emerging perspectives of immunomodulation

For many years atherosclerosis was believed to be the passive accumulation of cholesterol in vessel walls. Today the picture is more complex, as immune processes occur in atherogenesis. Considerable attention is focused on the particular role of adaptive immune responses orchestrated by T cell subsets. Since the role of Th1/Th2 balance and Th1 cell domination in atherogenesis is already known, the involvement of regulatory T lymphocytes and recently described Th17 cells raises new concerns. On one hand, each of these cells may specifically drive responses of vascular wall tissues and immune cells; however, they are subject to the control of a plethora of tissue- and pathogen-derived agents. Due to ineffective tissue regeneration, remodeling of the vascular wall occurs. The understanding of the immune regulatory network gives perspectives of innovative immunomodulatory therapies of atherosclerosis and the prevention of its complications, such as coronary artery disease.

Effect of statins on platelet function in patients with hyperlipidemia

Introduction It is generally assumed that cholesterol reduction by statins is the predominant therapeutic result underlying their beneficial effects in cardiovascular disease. However, the action of statins may be partially independent of their effects on plasma cholesterol levels, as they combine lipid lowering with positive effects on hemorheological conditions and endothelial function. We evaluated the impact of statin treatment on platelet adhesion to fibrinogen (spontaneous and ADP-activated), along with ADP, collagen or ristocetin-induced aggregation in type II hyperlipidemic patients. Material and methods The study group included 70 persons: 50 patients affected by type II hyperlipidemia without concomitant diseases and 20 healthy volunteers. The effects of 8-week statin treatment (atorvastatin 10 mg/day, simvastatin 20 mg/day, or pravastatin 20 mg/day) on platelet activation were evaluated. Results Regardless of the type of statin, a significant decrease in ADP-induced platelet aggregation was observed: for atorvastatin 50.6 ±12.8% vs. 41.1 ±15.8% (p < 0.05), for simvastatin 57.2 ±18.0% vs. 44.7 ±22.1% (p = 0.05), and for pravastatin 55.8 ±19.5% vs. 38.8 ±23.3% (p < 0.05). There was no significant effect of statins on collagen or ristocetin-induced platelet aggregation and adhesion. Conclusions Therapy with statins beneficially modifies ADP-induced platelet aggregation in patients with hyperlipidemia and does not affect spontaneous or ADP-induced platelet adhesion to fibrinogen and platelet aggregation induced by collagen or ristocetin.

Intensive statin therapy, used alone or in combination with ezetimibe, improves homocysteine level and lipid peroxidation to a similar degree in patients with coronary artery diseases

BACKGROUND Increase in the concentration of homocysteine is one of the risks of cardiovascular diseases. Coronary artery disease accompanied the increase of LDL cholesterol level and hipolipemic drugs are used in such treatments. Also these drugs have pleiotropic effects, which are not greatly known. The aim of that study is to compare the effect of three different hipolipemic therapies (rosuvastatin 15mg/d; atorvastatin 40mg/d; atorvastatin+ezetymibe 10mg/d+10mg/d) depending upon the concentration of homocysteine and lipid peroxidation in plasma of CAD patients with non-target LDL-cholesterol level. METHODS AND RESULTS The study involved 30 healthy subjects as well as 30 patients with angiographically confirmed coronary artery disease who despite at least 6 months hypolipidemic treatment did not achieve LDL-C <70mg/dl. The following parameters studied included homocysteine level, lipid peroxidation in plasma and lipidogram parameters. Our study showed increase of homocysteine level, lipid peroxidation in plasma, LDL-C concentration and total cholesterol level. After six months therapy, the following changes were observed in comparison to the values before therapy: decrease of homocysteine level in plasma - R15 20%, A40 26% and A+E 28%; decrease of lipid peroxidation in plasma - R15 31%, A40 27% and A+E 32%; decrease of LDL-C cholesterol level - R15 18%; A40 17% and A+E 33% and decrease of total cholesterol level - R15 9%, A40 15% and A+E 17%. CONCLUSION Our results suggest that intensive lipid-lowering therapy has a beneficial effect on certain parameters of the blood of CAD patients.

Recurrent syncope and hypocalcaemic cardiomyopathy as manifestations of Fahr's syndrome

In our report we would like to present a case of a 60-year-old patient with epileptic seizures, affective disturbances, only mild neurocognitive disorders and cardiomyopathy. A female patient was taken to the internal ward with a tentative diagnosis of recurrent syncope. Laboratory results disclosed severe hypocalcaemia, hypoparathyroidism, and hypothyroidism. An echocardiogram revealed left ventricle systolic dysfunction. Computed tomography revealed massive intracranial calcifications typical for Fahrs syndrome. Our patient demonstrated only mild neurological and psychiatric symptoms, but developed hypocalcaemic heart failure. It is possible that some cases of Fahrs syndrome remain undiscovered, particularly patients taken to internal wards with mild neurological or psychiatric signs.

IL-22 modulates inflammatory properties of human primary aortic smooth muscle cells

BACKGROUND IL-22 is expressed at barrier surfaces, which suggests its critical role in the maintenance of normal barrier homeostasis and tissue repair. IL-22 can both promote pathological inflammation and prevent the destruction of tissues. The functional outcomes of IL-22 on vascular smooth muscle cells, which are shown to regulate immune processes within the vascular wall and which are involved in certain pathologies, have not been analyzed. OBJECTIVES The effect of IL-22 on the expression of novel antiand pro-inflammatory and barrier disrupting cytokines, apoptosis and the expression of adhesive molecules in human primary aortic smooth muscle cells (AoSMC) was investigated. MATERIAL AND METHODS Human AoSMC were induced with IL-22 for 24 h in vitro. The influence of IL-22 on IL-35 subunits EBI3 and p35, IL-33, IFN-γ and VEGF mRNA expression in Ao-SMC were assessed using real-time PCR. Additionally, the surface expression of ICAM-1 and apoptosis of AoSMC were analyzed in the flow cytometer. RESULTS IL-22 caused a 2- and 3-fold increase of mRNA expression of the EBI3 and p35 IL-35 subunits, and a 40% decrease of IL-33 mRNA expression in AoSMC. Additionally, IL-22 decreased ICAM-1 expression on the surface of AoSMC by 30%. However, IL-22 affected neither IFN-γ and VEGF mRNA expression in AoSMC nor their apoptosis and viability. CONCLUSIONS Our data suggest that IL-22, which is released by Th22 and NK cells, may be an agent affecting the inflammatory response of AoSMC, and thus it may regulate immune homeostasis of the vascular wall.