Effect of Bezafibrate on Soluble Adhesion Molecules and Platelet Activation Markers in Patients With Connective Tissue Diseases and Secondary Hyperlipidemia

Abstract

We evaluated the plasma concentrations of soluble adhesion molecules, platelet activation markers, and platelet-derived microparticles (PMPs) in patients with connective tissue diseases who had secondary hyperlipidemia caused by long-term steroid administration (n = 22) before and after treatment with bezafibrate. There were differences in levels of platelet activation markers both before and after treatment (platelet CD62p: 15.11+/-2.03 vs 10.38+/-8.53%, P < 0.05; platelet CD63: 12.12+/-9.17 vs 9.90+/-7.20%, P < 0.05). There were also differences in the levels of PMPs and soluble adhesion molecules both before and after treatment (PMP: 514+/-273 vs 401+/-201 /10(4) platelet. P < 0.05; soluble vascular cell adhesion molecule-1: 724+/-191 vs 666+/-157 ng/mL, P < 0.01). After 6 months of treatment, serum lipid concentrations were reduced by 9% for total cholesterol (TC) and 32% for triglyceride (TG). The level of PMPs, activated platelets, and soluble adhesion molecules were all significantly decreased after treatment with bezafibrate. These findings suggest that bezafibrate may be useful for inhibiting both PMP-dependent and -independent vascular damage in patients with connective tissue diseases complaining of secondary hyperlipidemia.

Elevated levels of platelet microparticles are associated with disease activity in rheumatoid arthritis

“…These results confirm our hypothesis that PMPs are involved in the inflammatory processes of RA. Previous studies showed elevated numbers of PMPs in patients with symptoms of Raynaud's disease (one of whom had RA) and in patients with systemic lupus erythematosus (19, 20). Other inflammatory conditions have also been associated with PMPs (25, 27).…”

“…In summary, several observations support the theory that PMPs are involved in the inflammatory processes of rheumatic diseases. Until now, however, only 2 studies (one of which included only a single RA patient) dealt with this subject (19, 20). The aim of the present study was to investigate the level of plasma PMPs in patients with RA compared with healthy controls and to study the relationship between PMP levels and disease activity in RA.…”

Low-Density Lipoprotein-Lowering Medication and Platelet Function

“…Fibrinogen levels are also signifi cantly lowered after bezafi brate treatment, the effect being more marked in patients with hyperfi brinogenemia [91,92] , but no differences in platelet-fi brinogen binding were observed in a double-blind, placebo-controlled cross-over trial with 400 mg bezafi brate once daily [93] . The level of platelet microparticles, activated platelets, and soluble adhesion molecules were all significantly decreased after 6 months of treatment with bezafi brate [94] .…”

Role of Platelet-Derived Microvesicles As Crosstalk Mediators in Atherothrombosis and Future Pharmacology Targets: A Link between Inflammation, Atherosclerosis, and Thrombosis

“…Hence, in view of all these data statins may exert beneficial effects by inhibiting microvesicle generation and the triggering of MV-dependent mechanisms. Other cardioprotective agents that have an impact on pMV levels include calcium channel blockers (Nomura et al, 2005a,b), antioxidants such as vitamin C (Morel et al, 2003), and PPAR-pan agonists like bezafibrate (Kagawa et al, 2001). As several therapeutic drugs seem to influence the levels and composition of pMVs, the lowering of pMV load in the circulation might prove, at least in part, to be a novel therapeutic strategy for treatment.…”