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

• DOI: 10.1016/j.phrs.2006.08.005
• Publication Date: 2006-09-04T11:15:06Z
• Authors: V BLAHA; C ANDRYS; A SMAHELOVA; J KNIZEK; R HYSPLER; D SOLICHOVA; M BLAHA; Z ZADAK
• Keywords: Male; 2. Zero hunger; Lipopolysaccharide Receptors; Middle Aged; Ligands; Lipid Metabolism; 3. Good health; P-Selectin; 03 medical and health sciences; Cholesterol; 0302 clinical medicine; Diabetes Mellitus, Type 2; Heptanoic Acids; Atorvastatin; Humans; Female; Pyrroles; CD40 Antigens; Hydroxymethylglutaryl-CoA Reductase Inhibitors; E-Selectin; Chemokine CCL2

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.