The influence of statin monotherapy and statin-ezetimibe combined therapy on FoxP3 and IL 10 mRNA expression in patients with coronary artery disease.

BACKGROUND: FoxP3 is a marker of human T regulatory cells (Tregs), which are supposed to play an important role in the pathophysiology of atherosclerosis. Interleukin 10 (IL-10) is a cytokine with pleiotropic, immunoregulatory properties, produced mostly by Tregs and B regulatory cells. Due to their anti-inflammatory action, both Tregs and IL-10 are believed to inhibit plaque development and decrease atherosclerosis progression. The effect of hypolipidemic drugs - statins or ezetimibe - on FoxP3-positive Tregs and anti-inflammatory cytokines, such as IL-10, is still unclear. OBJECTIVES: The objective of the study was to investigate the effects of 3 different therapies of equivalent hypolipidemic activity: atorvastatin, rosuvastatin, and combination therapy of atorvastatin and ezetimibe on FoxP3-Tregs transcription factor and IL-10 mRNA expression in peripheral blood mononuclear cells (PBMCs) from patients with stable coronary artery disease (CAD). MATERIAL AND METHODS: Sixty-five patients with diagnosed CAD participated in the study. They were randomly assigned to 3 therapeutic groups: atorvastatin at a dose of 40 mg/day (A40 group); rosuvastatin 20 mg/day (R20 group); and atorvastatin 10 mg/day combined with ezetimibe 10 mg/day (A10+E10 group). After 1 month and 6 months of therapy, the mRNA expression for FoxP3 and IL-10 in PBMCs was evaluated using real-time polymerase chain reaction (RT-PCR) and lipid parameters. RESULTS: An improvement in lipid parameters was observed in each of the groups studied; however, hypolipidemic treatment did not induce any change in FoxP3 and IL-10 mRNA expression. After 6 months, an increase in FoxP3 mRNA expression was noted in A40 group as compared to R20 group. CONCLUSIONS: None of the therapies of equal hypolipidemic efficacy affected FoxP3 and IL-10 mRNA expression in patients with stable CAD.

Comparison of the effects of rosuvastatin monotherapy and atorvastatin-ezetimibe combined therapy on the structure of erythrocyte membranes in patients with coronary artery disease.

BACKGROUND: Abnormalities in the physical properties of the red blood cells (RBCs) membranes may underlie the defects that are strongly linked to cardiovascular diseases (CVD). The aim of the study was to compare the effects of two therapies of equal hipolipemic efficacy on the erythrocyte membrane fluidity, concentration of membrane cholesterol, lipids peroxidation and RBCs distribution witdh in patients with CVD. METHODS: The study included 44 patients with angiographic evidence of CVD, who despite previous 6-month hypolipemic therapy, did not achieve the concentration of LDL-C <70mg/dl. They were randomly assigned to: rosuvastatin 20mg/day (R20) and atorvastatin 10mg/day combined with ezetimibe 10mg/day (A10+E10). The membrane fluidity, the concentration of thiobarbituric acid reactive substances -TBARS, concentration of membrane cholesterol were evaluated after 6 months therapy. RESULTS: An improvement in lipid parameters was observed in each of the groups studied. In R20 the treatment resulted in 33% reduction concentrations of TBARS in serum, as well as in a decrease in membrane cholesterol by 16%, fluorescence anisotropy of TMA-DPH by 17.7%, fluorescence anisotropy of DPH by 2.8%. In A10+E10 the reduction of TBARS by 20.5% in serum, membrane cholesterol by 15.8% as well as a 14.25% increase in RBC membrane fluidity in the superficial layer (TMA-DPH) and decrease fluidity in the deep layer (DPH) were observed. CONCLUSION: Rosuvastatin increases the fluidity of erythrocyte membrane and decreases the TBARS in serum to greater extent than does equal hipolipemic combined therapy atorvastatin with ezetimibe.

The Effect of Combined Ezetimibe/Atorvastatin Therapy vs. Atorvastatin Monotherapy on the Erythrocyte Membrane Structure in Patients with Coronary Artery Disease: A Pilot Study.

BACKGROUND: Erythrocytes play an important role in atherogenesis. An excessive accumulation of cholesterol in erythrocyte membranes leads to disruption of the erythrocytes. OBJECTIVES: The aim of the study was to compare the effect of two different hypolipidemic therapies on the structure of erythrocyte membranes. MATERIAL AND METHODS: The study included 18 patients with angiographic confirmed coronary artery disease who, despite at least 6 months of hypolipidemic treatment, had not achieved LDL-C < 70 mg/dL and 18 healthy individuals as the control group. The following parameters were studied: total cholesterol level and erythrocyte membrane fluidity, lipid peroxidation, SH groups in membrane protein and plasma lipids. RESULTS: We observed a decrease in TC (20%), LDL-C (35%), level of lipid peroxidation (25%) and total cholesterol in erythrocytes (23%), and an increase in HDL-C (8%) and erythrocyte membrane fluidity of subsurface layers (14%) after 6 months of 10 mg atorvastatin + 10 mg ezetimibe therapy, in comparison with healthy controls. In the group treated with 40 mg atorvastatin for 6 months, decreased LDL-C (23%), lipid peroxidation (37%) and membrane cholesterol concentration (18%) was noted, as well as an increase in erythrocyte membrane fluidity in the subsurface layers (12%). CONCLUSIONS: Both the combination therapy and the monotherapy lead to an improvement of erythrocyte membrane structure, whose parameters reached values close to those in the control healthy group.

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.

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.

Disorders of erythrocyte structure and function in hypertensive patients.

BACKGROUND: The prevalence of hypertension is growing at an alarming rate. Increasing attention is being focussed on the oxidative stress accompanying this disease. In this study we examined the impact of this disease on some parameters of erythrocytes and human blood plasma. MATERIAL/METHODS: We examined the impact of hypertension on some parameters of erythrocytes and human plasma. The study involved 13 patients with hypertension and 19 healthy subjects. We determined lipid peroxidation, SH groups concentration, antioxidants enzymes activity, ATPase activity, total antioxidant capacity, total cholesterol level and erythrocyte membrane fluidity. RESULTS: We found an increased level of lipid peroxidation and the concentration of SH groups in membrane proteins in patients with hypertension, and a decrease in the activity of catalase and superoxide dysmutase. No changes were observed in glutathione peroxidase and ATPase activity, level of total antioxidant capacity, total cholesterol level and fluidity of erythrocyte membranes. CONCLUSIONS: These results suggest the existence of an impaired oxidative balance in hypertensive human erythrocytes.