RGD Reference Report - Divergent effects of matrix metalloproteinases 3, 7, 9, and 12 on atherosclerotic plaque stability in mouse brachiocephalic arteries. - Rat Genome Database

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Divergent effects of matrix metalloproteinases 3, 7, 9, and 12 on atherosclerotic plaque stability in mouse brachiocephalic arteries.

Authors: Johnson, JL  George, SJ  Newby, AC  Jackson, CL 
Citation: Johnson JL, etal., Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15575-80. Epub 2005 Oct 12.
RGD ID: 1582354
Pubmed: PMID:16221765   (View Abstract at PubMed)
PMCID: PMC1266110   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0506201102   (Journal Full-text)

Matrix metalloproteinases (MMPs) are thought to be involved in the growth, destabilization, and eventual rupture of atherosclerotic lesions. Using the mouse brachiocephalic artery model of plaque instability, we compared apolipoprotein E (apoE)/MMP-3, apoE/MMP-7, apoE/MMP-9, and apoE/MMP-12 double knockouts with their age-, strain-, and sex-matched apoE single knockout controls. Brachiocephalic artery plaques were significantly larger in apoE/MMP-3 and apoE/MMP-9 double knockouts than in controls. The number of buried fibrous layers was also significantly higher in the double knockouts, and both knockouts exhibited cellular compositional changes indicative of an unstable plaque phenotype. Conversely, lesion size and buried fibrous layers were reduced in apoE/MMP-12 double knockouts compared with controls, and double knockouts had increased smooth muscle cell and reduced macrophage content in the plaque, indicative of a stable plaque phenotype. ApoE/MMP-7 double knockout plaques contained significantly more smooth muscle cells than controls, but neither lesion size nor features of stability were altered in these animals. Hence, MMP-3 and MMP-9 appear normally to play protective roles, limiting plaque growth and promoting a stable plaque phenotype. MMP-12 supports lesion expansion and destabilization. MMP-7 has no effect on plaque growth or stability, although it is associated with reduced smooth muscle cell content in plaques. These data demonstrate that MMPs are directly involved in atherosclerotic plaque destabilization and clearly show that members of the MMP family have widely differing effects on atherogenesis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
arteriosclerosis  ISOMmp12 (Mus musculus)1582354; 1582354 RGD 
arteriosclerosis  IAGP 1582354 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp12  (matrix metallopeptidase 12)

Genes (Mus musculus)
Mmp12  (matrix metallopeptidase 12)

Genes (Homo sapiens)
MMP12  (matrix metallopeptidase 12)


Additional Information