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- January 6, 2009 |
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CME on Diabetes is a website built to transmit top-level CME conferences given by international experts in endocrinology, insulin resistance, prediabetes, metabolic syndrome and type 2 diabetes. More than 2.6 million slides have been viewed since the website launch. Thank you for your continued support and commitment!
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"Clofibrate Reduces Human Platelet Aggregation: A Possible PPAR-α Mediated Effect"Dr. Manish Khanolkar (biography)
English - 2005-04-15 - 24 minutes
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Summary :
Fibrates are PPARα agonists, increasingly used to treat a dyslipidemia characterized by elevated triglycerides and a low HDL-Cholesterol as is known to occur in individuals with the metabolic syndrome. Fibrates also appear to influence a number of emerging risk factors, including hemostatic and inflammatory markers, which may contribute to their cardioprotective effects. Platelet hyperaggregability has been described in individuals with the metabolic syndrome and plays an important role in atherothrombosis. Recent studies have shown that human platelets express functional PPARγ receptors and that PPARγ agonists are capable of inhibiting platelet activation. We demonstrated the presence of PPARα receptors in human platelets using flow cytometry and western blotting. We subsequently conducted an invitro study assessing the effects of clofibrate on ADP induced platelet aggregation in whole blood from healthy volunteers using whole blood impedance aggregometry. Increasing platelet aggregation between the two electrodes produced increasing electrical impedance displayed as a function of time on a chart recorder allowing its quantification in ohms. Preincubating blood with PPARα agonist, clofibrate resulted in a significant reduction in ADP induced platelet aggregation (p<0.01, paired t-test). This is the first study to demonstrate the presence of PPARα receptors in human platelets.This study further supports the potential likely benefits of clofibrate in reducing cardiovascular risk. Further mechanistic studies are required to explore the precise molecular mechanisms involved and to determine clinical relevance of these findings.
Learning objectives :
After viewing this presentation the participant will be able to discuss:
- Platelet aggregation in atherothrombosis and type 2 diabetes;
- The expression of PPAR-alpha and PPAR-gamma in platelets;
- The effects of clofibrate and conjugated linoleic acid (CLA) on platelet aggregation;
- The role of PPAR-alpha in platelet aggregation;
Bibliographic references :
P. Ferroni, S. Basili, A. Falco and G. Davì Platelet activation in type 2 diabetes mellitus Journal of Thrombosis and Haemostasis Volume 2, Issue 8, Page 1282-1291, August 2004
Filiz Akbiyik, Denise M. Ray, Kelly F. Gettings, Neil Blumberg, Charles W. Francis, and Richard P. Phipps Human bone marrow megakaryocytes and platelets express PPAR , and PPAR agonists blunt platelet release of CD40 ligand and thromboxanes Blood, Sep 2004; 104: 1361 - 1368.
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