Plasma RANTES Levels Research Articles

Investigation of the Correlation Between the Polymorphism/Expression Level of RANTES and Its Receptor CCR5 Gene Promoter and Type 2 Diabetes Mellitus

This study aimed to explore relationship among RANTES -28 (rs2280788) C/G polymorphism or CCR5 59029 (rs1799987) A/G polymorphism, level of self-expression, and type 2 diabetes mellitus (T2DM). Clinical data were collected from 92 subjects with normal blood glucose (NC) and 97 patients with T2DM (DM). CCR5 levels on the surface of monocyte/lymphocyte and plasma RANTES levels were detected by flow cytometry. TaqMan real-time fluorescent quantitative PCR was used to detect genetic polymorphisms of RANTES rs2280788 and CCR5 rs1799987. There were no significant differences in frequencies of CCR5 rs1799987 genotype and A/G allele and frequencies of RANTES rs2280788 genotype and C/G allele, between subjects in NC and DM group (P > 0.05). Plasma RANTES level in DM group was significantly lower than NC group (P < 0.05), and difference came from patients with T2DM using insulin and subjects with normal blood glucose. CCR5 levels on the surface of monocytes and lymphocytes of patients in DM group were higher than NC group (P < 0.05). There was no significant difference in CCR5 level on the surface of monocytes and lymphocytes (or plasma RANTES level) among different genotypes of CCR5 rs1799987 (or RANTES rs2280788) (P > 0.05). RANTES level was positively correlated with age and TC and negatively correlated with diabetes course and HbA1c. CCR5 level on the surface of monocytes was positively correlated with drinking years, HbA1c, course of diabetes, and negatively correlated with TC. CCR5 on lymphocyte surface was positively correlated with diabetes course, smoking years, HbA1c, and negatively correlated with LDL, TC, HDL (P < 0.05). RANTES -28 (rs2280788) C/G polymorphism or CCR5 59029 (rs1799987) A/G polymorphism may not be associated with T2DM of Han nationality in Kunming and cannot affect RANTES and CCR5 expression. RANTES and CCR5 levels may be related to T2DM but may also be affected by age, blood lipids, HbA1c, diabetes course, drugs, and other factors.

Treatment With Ezetimibe Plus Low-Dose Atorvastatin Compared With Higher-Dose Atorvastatin Alone: Is Sufficient Cholesterol-Lowering Enough to Inhibit Platelets?

We sought to test the platelet inhibitory and anti-inflammatory effects of a higher statin dosage compared with combined treatment with ezetimibe plus a low statin dose. Reducing the level of low-density lipoprotein cholesterol (LDL-C) with statins induces important pleiotropic effects such as platelet inhibition. An insufficient LDL-C reduction often is treated with ezetimibe, an intestinal cholesterol absorption inhibitor, in combination with a low statin dose. It is not known whether this combination therapy has the same pleiotropic effects as a statin monotherapy. Fifty-six patients with coronary artery disease were assigned randomly to receive either 40 mg/day of atorvastatin or 10 mg/day of ezetimibe plus 10 mg/day of atorvastatin for 4 weeks. The levels of LDL-C, platelet activation markers after stimulation, platelet aggregation, and plasma chemokine levels (i.e., regulated on activation normally T-cell expressed and secreted [RANTES]) were measured before and after changing lipid-lowering medication. Platelet activation markers (P-selectin) after stimulation (adenosine diphosphate) were reduced by 40 mg/day of atorvastatin (-5.2 +/- 1.6 arbitrary units) but not by ezetimibe plus low-dose atorvastatin (2.1 +/- 1.8 arbitrary units; p < 0.005) despite a similar reduction of LDL-C (atorvastatin -1.01 +/- 0.18 mmol/l vs. ezetimibe plus atorvastatin -1.36 +/- 0.22 mmol/l, p = NS). Thrombin receptor-activating peptide-induced platelet aggregation as well as plasma RANTES levels were reduced by 40 mg/day of atorvastatin but not by ezetimibe plus low-dose atorvastatin. Platelet reactivity and a proinflammatory chemokine were reduced more by the higher atorvastatin dose than by ezetimibe plus low-dose atorvastatin. In patients with coronary artery disease, it might be important to combine ezetimibe with higher statin dosages to benefit from cholesterol-independent pleiotropic effects.