Statin drugs and dietary isoprenoids downregulate protein prenylation in signal transduction and are antithrombotic and prothrombolytic agents

Biochemistry (Mosc). 2002 Jan;67(1):85-91. doi: 10.1023/a:1013956215394.

Abstract

Statins 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.

Publication types

  • Review

MeSH terms

  • Animals
  • Anticholesteremic Agents / pharmacology*
  • Down-Regulation*
  • Fibrinolytic Agents / pharmacology*
  • Guanosine Triphosphate / metabolism
  • Humans
  • Models, Biological
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Polyisoprenyl Phosphates / metabolism*
  • Protein Prenylation
  • Receptor, PAR-1
  • Receptors, Thrombin / metabolism
  • Signal Transduction
  • Thrombin / metabolism
  • Thromboplastin / metabolism
  • Up-Regulation

Substances

  • Anticholesteremic Agents
  • Fibrinolytic Agents
  • Plasminogen Activator Inhibitor 1
  • Polyisoprenyl Phosphates
  • Receptor, PAR-1
  • Receptors, Thrombin
  • Guanosine Triphosphate
  • Thromboplastin
  • Thrombin