Modification of platelet shape change parameter by oxidized lipoprotein from beta-thalassemia/Hemoglobin E.

BACKGROUND: Beta-thalassemia/Hemoglobin E (beta-thal/Hb E) is a congenital hemolytic anemia that is prevalent in Thailand Pulmonary arterial occlusion is the cause of morbidity and mortality in these patients. Abnormality of platelets has been implicated as pathogenesis of this condition. However the blood-borne factors that induce platelet activation are not identified Recently, oxidized low-density lipoproteins (ox-LDLs) had been identified in thalassemic blood. OBJECTIVE: Identify whether oxidized LDL is the blood bone factor that induce platelet activation in beta-thal/Hb E patients. MATERIAL AND METHOD: Platelet activation was measured by monitoring platelet shape change parameter using plasma-free human platelets. The shape change parameter was monitored following exposure to normal LDL, oxidized LDL, and thalassemic LDL. RESULTS: Oxidized LDL, but not the native LDL and thalassemic LDL, showed platelet activation activity. Oxidation of thalassemic LDL with copper give rise to oxidized LDL with platelet activating activity. However less copper was needed by LDL from splenectomized beta-thal/Hb E patients than those from nonsplencectomized beta-thal/Hb E patients. CONCLUSION: LDL from splenectomized beta-thal/Hb E patients is more susceptible for oxidation and gives rise to oxidized-LDL that plays an important role in thrombosis event in these patients.

Atorvastatin attenuates TLR4-mediated NF-κB activation in a MyD88-dependent pathway.

Antigen presenting cells such as dendritic cells and macrophages have recently been detected in atherosclerotic plaques. Toll-like receptors expressed on the surface of these cells, have been implicated in ongo-ing inflammatory responses in the plaques. In this study, we investigated the anti-inflammatory effect of atorvas-tatin, a lipid lowering drug, via Toll-like receptor 4 (TLR4) in vitro, employing murine pro-B cell lines transfected with hTLR4/MD2 and MyD88/hTLR4/MD2 systems. The results showed that atorvastatin at 10 μM significantly attenu-ated NF-κB activation within 24 hours while at lower doses of 0.1 and 1 μM, treatment time had to be prolonged up to 48 hours for a significant inhibition to occur. The inhibition of NF-κB was also observed in a cell line co-transfected with MyD88 and TLR4 suggesting that the attenuation of NF-κB by atorvastatin occurred in a MyD88 dependent fashion.

Modification of platelet shape change parameter by modified phospholipids in oxidized LDL.

BACKGROUND: It is believed that the oxidatively modified lipoproteins play a critical role in activating platelets and is a contributing factor in the etiology of a number of cardiovascular-related diseases. OBJECTIVE: Identify the active component(s) of oxidized LDL that initiated shape change in plasma-free human platelets prepared by a gel filtration method Material and Method: Shape change parameter of platelets was monitored following exposure platelets to LDL, copper sulfate-oxidized LDL, and different types of lipids extracted of the corresponding LDL. RESULTS: Oxidized LDL, but not native LDL, increased the shape-change parameter in a concentration-dependent manner Specifically, phosphatidyl serine from oxidized LDL was responsible for this effect. CONCLUSION: Oxidized phospholipids generated during the oxidative modification of LDL are likely to be the active components responsible for changes in platelet function.