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Statin drugs and dietary isoprenoids downregulate protein prenylation in signal transduction and are antithrombotic and prothrombolytic agents Fenton JW 2nd; Jeske WP; Catalfamo JL; Brezniak DV; Moon DG; Shen GXBiochemistry (Mosc) 2002[Jan]; 67 (1): 85-91Statins and various isoprenoids of dietary origins inhibit L-mevalonic acid synthesis, which in turn downregulates cholesterol and various other dependent substances, including farnesyl- and geranylgeranyl-conjugated proteins involved in cell signaling processes. Such signaling processes are stimulated by protease-activated receptor-1 (PAR-1), which upon activation, causes the expression of various substances including tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1). Tissue factor promotes thrombin generation, where thrombin stimulates a variety of cellular processes, as well as activating PAR-1 to produce more thrombin. Statins downregulate TF mitigating thrombin generation and also downregulate PAI-1, which normally consumes tissue plasminogen activator (tPA). In the absence of PAI-1, tPA activates plasminogen to generate plasmin. Thus, statins behave as antithrombotic agents and prothrombolytic agents.|*Down-Regulation[MESH]|Animals[MESH]|Anticholesteremic Agents/*pharmacology[MESH]|Fibrinolytic Agents/*pharmacology[MESH]|Guanosine Triphosphate/metabolism[MESH]|Humans[MESH]|Models, Biological[MESH]|Plasminogen Activator Inhibitor 1/metabolism[MESH]|Polyisoprenyl Phosphates/*metabolism[MESH]|Protein Prenylation[MESH]|Receptor, PAR-1[MESH]|Receptors, Thrombin/metabolism[MESH]|Signal Transduction[MESH]|Thrombin/metabolism[MESH]|Thromboplastin/metabolism[MESH]|Up-Regulation[MESH] |
