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.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/17495 |
| Date | 30 July 2009 |
| Creators | Blankier, Shawn Adam |
| Contributors | Ito, Shinya, Yeung, Rae S. M. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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