Rosuvastatin reduced deep vein thrombosis in ApoE gene deleted mice with hyperlipidemia through non-lipid lowering effects.

INTRODUCTION: Statins, particularly rosuvastatin, have recently become relevant in the setting of venous thrombosis. The objective of this study was to study the non-lipid lowering effects of rosuvastatin in venous thrombosis in mice with hyperlipidemia. MATERIALS AND METHODS: An inferior vena cava ligation model of venous thrombosis in mice was utilized. Saline or 5mg/kg of rosuvastatin was administered by gavage 48hs previous to thrombosis. Blood, the inferior vena cava, thrombus, and liver were harvested 3, 6hours, and 2days post-thrombosis. Thrombus weight, inflammatory markers, and plasminogen activator inhibitor-1 expression and plasma levels were measured. Also, neutrophil migration to the IVC was assessed. RESULTS: Rosuvastatin significantly decreased thrombus weight, plasminogen activator inhibitor-1 expression and plasma levels, expression of molecules related to the interleukin-6 pathway, and neutrophil migration into the vein wall. CONCLUSIONS: This work supports the beneficial effects of rosuvastatin on venous thrombosis in mice with hyperlipidemia, due to its non-lipid lowering effects.

The effect of lymphatic oedema on the uptake of colloids to the lymph nodes.

The majority of pathological conditions of the lymphatic system can result in some degree of lymphoedema, which in turn causes a reduced rate of lymph flow. In some cases, such as when nodes are invaded by tumour metastases, blockage of the lymphatic vessels may occur. In order to investigate the effect of such pathology on nanosphere uptake in regional lymph nodes, the fate of model polystyrene nanospheres, surface modified with block co-polymers of the poloxamine series, was determined following subcutaneous administration in a rat model with lymphoedema (induced by the administration of lambda-carrageenan). A drastic reduction of injection site drainage and lymph node uptake of nanospheres was observed in the inflammation model compared to control animals. The observations suggest that biodegradable nanospheres based on these will be suitable for the detection of oedema in the lymphatic system.

Surface engineered nanospheres with enhanced drainage into lymphatics and uptake by macrophages of the regional lymph nodes.

The concept of steric stabilization as used in colloid science is applied to carefully manipulate the drainage and lymphatic distribution of subcutaneously administered model polystyrene nanospheres. A wide range of synthetic polyoxyethylene (POE)/polyoxypropylene (POP) block co-polymers of poloxamine and poloxamer series have been used to produce sterically stabilized nanospheres. We have found a correlation between the length of the stabilizing POE chains of the block co-polymers and nanosphere drainage and passageway across tissue lymph interface in dermal lymphatic capillaries in the rat footpads; the longer the POE chains, the faster the particle drainage. Nanospheres conditioned with block co-polymers of POE chains of 5-15 ethylene oxide units are effectively opsonized in lymphatics; a process which dramatically enhances sequestration (up to 40% of the administered dose) by macrophages of the regional lymph nodes. If the dimensions of the stabilizing POE chains of the poloxamines and poloxamers exceed the range of the Van der Waals force of attraction, opsonization fails to occur and rapidly drained engineered vehicles escape clearance by macrophages of the regional nodes, reach the systemic circulation and remain in the blood for prolonged periods. These observations suggest that a lymphatic delivery composition based on polymer-coated particles will be advantageous for many applications in clinical and experimental medicine.