We conducted a study to assess the effect of rosuvastatin use on fibrinolysis in patients with previous venous thromboembolism (VTE). This was a post hoc analysis within the STAtins Reduce... Show moreWe conducted a study to assess the effect of rosuvastatin use on fibrinolysis in patients with previous venous thromboembolism (VTE). This was a post hoc analysis within the STAtins Reduce Thrombophilia (START) study (NCT01613794). Plasma fibrinolytic potential, fibrinogen, plasmin inhibitor, plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) were measured before and after four weeks of rosuvastatin or no treatment in participants with prior confirmed VTE, after ending anticoagulant therapy. In the non-rosuvastatin group (n = 121), plasma fibrinolytic potential and individual fibrinolysis parameters did not change at the end of the study versus the baseline, whereas in the rosuvastatin group (n = 126), plasma fibrinolytic potential increased: the mean clot lysis time decreased by 8 center dot 75 min (95% CI -13 center dot 8 to -3 center dot 72), and plasmin inhibitor levels and TAFI activity were lower at the end of the study (-0 center dot 05 U/ml; 95% CI -0 center dot 07 to -0 center dot 02 and -4 center dot 77%; 95% CI -6 center dot 81 to -2 center dot 73, respectively). PAI-1 levels did not change and fibrinogen levels were 0 center dot 17 g/l (95% CI 0 center dot 04-0 center dot 29) higher. In participants with prior VTE, rosuvastatin use led to an increased fibrinolytic potential compared with non-statin use. Our findings support the need for further studies on the possible role for statins in the secondary prevention of VTE. Show less
Post, S.; Post, M.C.; Branden, B.J. van den; Eefting, F.D.; Goumans, M.J.; Stella, P.R.; ... ; Doevendans, P.A. 2012
Activation of microglia, the macrophages of the central nervous system, is a key element in multiple sclerosis (MS) lesion development and is characterized by enhanced expression of both classes of... Show moreActivation of microglia, the macrophages of the central nervous system, is a key element in multiple sclerosis (MS) lesion development and is characterized by enhanced expression of both classes of major histocompatibility complex (MHC) molecules. This enhanced expression results from increased levels of several transcription factors involved in MHC gene expression. In addition, microglial activation in MS is characterized by enhanced motility. We show that the expression of the chemokine receptor CCR5, a mediator of cell movement, is increased on microglia, macrophages and astrocytes in MS lesions. Additionally, we have determined that CCR5 transcription is regulated by the transcription factor CREB-1, which is also involved in MHC gene expression, and is highly expressed in MS lesions. Because of their immunomodulatory properties, statins (cholesterol lowering drugs) are recently being considered as a possible treatment for MS. We have determined that statins decrease expression of amongst others MHC and CCR5 molecules by inhibiting the transport of these molecules to the cell surface. In addition, we show that statins reduce the motility of microglia and inhibit the differentiation of blood-derived monocytes into dendritic cells, indicating that statins indeed affect critical immune functions and might prove to be beneficial for treatment of MS patients. Show less
