Atherogenesis involves the migration of leukocytes into vascular subendothelial space, a process mediated by endothelial and leukocyte cell adhesion molecules. Endothelial molecules are assessed indirectly via serum levels, but leukocyte molecules can be assessed directly. We have therefore hypothesized that leukocyte adhesion molecules are altered to a greater degree in hypercholesterolemia than serum endothelial adhesion molecules. We examined 29 subjects with hypercholesterolemia and 27 controls at baseline and after 12 weeks of atorvastatin treatment (20 mg/day). Expression of leukocyte integrins CD11a, CD11b, CD18, and CD49d and of L-selectin was measured by flow cytometry. Serum ICAM-1, E-selectin and von Willebrand factor were measured by ELISA. Expression of leukocyte adhesion molecules was significantly higher in patients at baseline than in the controls, except for CD11a. Expression significantly decreased after atorvastatin in most adhesion molecules except for CD11b. In contrast, there was no effect of hypercholesterolemia and/or atorvastatin on the serum endothelial molecules. Leukocyte but not endothelial adhesion molecules were influenced by hypercholesterolemia and by lipid lowering treatment. Leukocyte molecules may therefore be a more sensitive marker of atherogenesis than endothelial molecules. Our results support the role of increased leukocyte adhesiveness in atherogenesis., T. Štulc, M. Vrablík, Z. Kasalová, I. Marinov, H. Svobodová, R. Češka., and Obsahuje bibliografii a bibliografické odkazy
Lipoprotein(a) [Lp(a)] comprises of an LDL particle and apolipoprotein(a) [apo(a)] and its elevated levels are considered a risk factor for atherosclerosis. The aim of our study was to find out whether elevated Lp(a) levels are associated with increased risk of atherosclerosis in patients with multiple other risk factors. We further tested the association of three polymorphisms of the apo(a) gene promoter with Lp(a) levels. No significant correlation was detected between Lp(a) levels and lipid and clinical parameters tested. The study demonstrated a significantly (p=0.0219) elevated Lp(a) level (mean 28±35 mg/dl, median 0.14) in patients with coronary heart disease (CHD). In a group with premature CHD the correlation was not significant anymore. There was a significant correlation between polymorphic loci of the promoter region of apo(a) gene and Lp(a) levels (+93C>T, p=0.0166, STR, p<0.0001). Our study suggests that elevated Lp(a) level is an independent risk factor of CHD in carriers of other important CHD risk factors. Observed association of sequence variants of the promoter of apo(a) gene with Lp(a) levels is caused in part due to linkage to a restricted range of apo(a) gene length isoforms., L. Zlatohlávek, K, Zídková, M. Vrablík, T. Haas, M. Prusíková, H. Svobodová, R. Češka., and Obsahuje bibliografii a bibliografické odkazy
Diabetes mellitus is associated with a number of prothrombotic abnormalities, and correction of these abnormalities might translate into the reduction of cardiovascular risk. Glitazones improve endothelial function and reduce inflammation, but much less is known about their effect on thrombogenic factors. We have therefore studied the effect of rosiglitazone on leukocyte and soluble thrombogenic markers in patients with type 2 diabetes mellitus. Thirty-three subjects with type 2 diabetes and 32 normal controls were included; patients were examined at baseline and after 5 months of rosiglitazone treatment (4 mg/day). We measured leukocyte-platelet aggregates and leukocyte expression of either P-selectin glycoprotein ligand 1 (PSGL-1) or receptor for urokinase-type plasminogen activator (uPAR) using flow cytometry, as well as several circulating soluble thrombogenic markers by ELISA method. Leukocyte expression of uPAR and PSGL-1 was significantly higher in patients than in controls. Leukocyte-platelet aggregates and leukocyte expression of uPAR and PSGL-1 significantly decreased after rosiglitazone. There was also significant decrease in CRP and fibrinogen levels, but there was no effect of diabetes and/or rosiglitazone on other circulating molecules. In conclusions, we observed a substantial improvement in the expression of thrombogenic markers on leukocytes after rosiglitazone treatment, suggesting the novel antithrombotic effects of rosiglitazone., H. Svobodová ... [et al.]., and Obsahuje seznam literatury