title: Effect of atorvastatin on soluble CD14, CD40 Ligand, sE- and sP-selectins and MCP-1 in patients with type 2 diabetes mellitus: relationship to cholesterol turnover.
abstract: Metabolic abnormalities frequently associated with type 2 diabetes, feature besides endothelial dysfunction a novel factor of low cholesterol absorption and high cholesterol synthesis. We hypothesized an association between endothelial dysfunction and disturbances in cholesterol turnover, predisposing advanced atherosclerosis in patients with type 2 diabetes. We studied 75 patients: 30 with type 2 diabetes, 30 non-diabetic subjects with a history of cardiovascular disease, and 15 healthy subjects. Plasma sterols, soluble adhesion molecules sCD14, sCD40 Ligand, monocyte chemo-attractant protein-1 (MCP-1), sE- and sP-selectins were measured with and without atorvastatin therapy. The diabetic patients showed significantly higher levels of lathosterol and lower levels of sitosterol and campesterol. Non-diabetic subjects showed no significant differences in non-cholesterol based sterols. Plasma levels of hsCRP, sE- and sP-selectins and MCP-1 were significantly increased in patients with diabetes. The plasma levels of sCD40L correlate significantly with clinical parameters of BMI and glycaemia, and the plasma levels of sP-selectin correlate significantly with parameters of glycaemia and HbA(1c). The diabetic patients without statin therapy showed a significant correlation of sE-selectin with the marker of cholesterol absorption-sitosterol and sitosterol/cholesterol ratio. The diabetic patients without statin therapy showed a significant inverse correlation of sP-selectin with the marker of cholesterol synthesis-lathosterol. Both relationships disappeared with statin treatment. We conclude that endothelial dysfunction in obese patients with type 2 diabetes mellitus and cardiovascular disease associates with obesity and glycaemic control. The relation of parameters of endothelial dysfunction (such as sP-selectin and sE-selectin) with cholesterol synthesis and absorption may be influenced by reverse cholesterol transport.
authors.affiliation: Department of Metabolic Care and Gerontology, University Hospital Hradec Králové and Medical Faculty Charles University in Hradec Králové, Sokolská 581, 50005 Hradec Králové, Czech Republic. blaha@lfhk.cuni.cz
authors.forename: Vladimír
authors.initials: V
authors.lastname: Bláha
authors.forename: Ctirad
authors.initials: C
authors.lastname: Andrýs
authors.forename: Alena
authors.initials: A
authors.lastname: Smahelová
authors.forename: Jirí
authors.initials: J
authors.lastname: Knízek
authors.forename: Radomír
authors.initials: R
authors.lastname: Hyspler
authors.forename: Dagmar
authors.initials: D
authors.lastname: Solichová
authors.forename: Milan
authors.initials: M
authors.lastname: Bláha
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Zadák
mesh_terms: D000069059:Atorvastatin; D019013:CD40 Antigens / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D019040:E-Selectin / Q000378:metabolism*; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008024:Ligands; D050356:Lipid Metabolism / Q000187:drug effects; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology*
chemical_list: C111835:CCL2 protein, human; D019013:CD40 Antigens; D018932:Chemokine CCL2; D019040:E-Selectin; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D019007:P-Selectin; D011758:Pyrroles; D002784:Cholesterol; D000069059:Atorvastatin