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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/17495

Title: HMG-CoA Reductase Inhibition Reduces T-cell Activation, TNFα Production, and MMP-9 Gene Expression in a Superantigen-mediated Mouse Model of Kawasaki Disease
Authors: Blankier, Shawn Adam
Advisor: Ito, Shinya
Yeung, Rae S. M.
Department: Pharmaceutical Sciences
Keywords: Kawasaki Disease
Statins
Issue Date: 30-Jul-2009
Abstract: Kawasaki disease (KD) is a multisystem vasculitis leading to coronary artery aneurysm formation. In a superantigen-mediated murine model of KD, the development of coronary arteritis is mediated by T-cells through the production of TNFα. TNFα localizes to the coronary arteries, where it induces the expression of MMP-9, resulting in the breakdown of elastin and the formation of aneurysms. Statins have been recently shown to have anti-inflammatory and immunomodulatory properties as a result of the inhibition of small GTPases. In our murine model of KD, atorvastatin treatment inhibits superantigen mediated T- cell proliferation and cytokine production, including IL-2 and TNFα. Additionally, statin treatment inhibits TNFα-mediated MMP-9 production by vascular smooth muscle cells, through inhibition of the MEK/ERK pathway. Thus, statins modulate each of the critical steps in the pathogenesis of KD in a disease model, suggesting that statin use could alter the outcome and prognosis of children suffering with this disease.
URI: http://hdl.handle.net/1807/17495
Appears in Collections:Master
Leslie L. Dan Faculty of Pharmacy - Master theses

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