[Back to Number 1 ToC] [Back to Journal Contents] [Back to Biokhimiya Home page]
[View Full Article] [Download Reprint (PDF)]

REVIEW: Statin Drugs and Dietary Isoprenoids Downregulate Protein Prenylation in Signal Transduction and Are Antithrombotic and Prothrombolytic Agents

J. W. Fenton, II1,2*, W. P. Jeske3, J. L. Catalfamo4, D. V. Brezniak1, D. G. Moon5, and G. X. Shen6

1New York State Department of Health, Wadsworth Center, Albany, NY 12201-0509 USA; fax: 518-473-7082 or 2900; E-mail: brezniak@wadsworth.org

2Department of Physiology and Cell Biology and Department of Biochemistry and Molecular Biology, Albany Medical College, Albany, NY 12208 USA

3Cardiovascular Institute, Loyola University Medical Center, Maywood, IL 60153 USA

4College of Veterinary Medicine, Cornell University, Ithaca, NY 14852 USA

5Department of Biology, Albany College of Pharmacy, Albany, NY 12208 USA

6Departments of Internal Medicine and Physiology, University of Manitoba, Winnipeg, MB, R3E 3I7 Canada

* To whom correspondence should be addressed.

Received May 22, 2001; Revision received June 20, 2001
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.
KEY WORDS: statins, dietary isoprenoids, protein prenylation inhibition, protease-activated receptor mitigation, thrombin generation downregulation, plasmin generation upregulation