Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.551288
Title: The expression of matrix metalloproteinases in macrophage phenotypes
Author: Huang, Wei-Chun
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2011
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Abstract:
Macrophages, matrix metalloproteinases (MMPs) and tissue inhibitor of MMPs (TIMPs) are key factors in atherosclerotic plaque formation and plaque rupture, both of which are driven by macrophage accumulation and activation. The thesis investigated whether distinct phenotypes of macrophages may play different roles in MMP or TIMP expression during inflammation or plaque formation. The results showed that classically activated Ml macrophages significantly up-regulated MMP-l, MMP-3, MMP-7, MMP-IO, MMP-12, MMP-14 and MMP-25 and down-regulated TIMP-3, which suggests a strong increase in matrix-degrading potential. Patterns of response to classical activation in vitro are dominated by LPS and pro-inflammatory cytokines, only MMP-12, MMP-14 and MMP-25 expressions being partly affected by interferon-y. On the other hand, alternatively activated M2 macrophages strongly up-regulated MMP-II, MMP-12 and MMP-25, and this was accompanied by lower expression of many other MMPs and greater expression of TIMP-3. Hence alternative activation may rather selectively increase the potential for elastolysis by MMP-12, without promoting degradation of other matrix components. The MMP expression stimulated by classical activation depended on activation of mitogen activated protein kinases, phosphinositide-3 kinase, and inhibitor of K.8 kinase-2. In addition, MMP-l, and MMP-I0 co-localised with nuclear localised NF-KB in human atherosclerotic plaques. Furthermore, unstable plaques have higher COX-2, MMP-I, MMP-3, MMP-IO and MMP-14 expression in foam cell macro phages when compared to stable human coronary atherosclerotic plaques. By contrast, stable plaques had higher expression of the M2 marker, CD206, and TIMP-3 than human unstable plaques. In conclusion, Ml macrophages selectively increase the balance of several MMPs over TIMPs in macrophages in vitro and in unstable plaques, an example of inflammation in vivo. However, only limited groups of MMPs and TIMP-3 were significantly over-expressed in M2 macrophages.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.551288  DOI: Not available
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