ApoE knockout mice expressing human matrix metalloproteinase-1 in macrophages have less advanced atherosclerosis

Vincent Lemaître, Timothy K. O'Byrne, Alain C. Borczuk, Yasunori Okada, Alan R. Tall, Jeanine D'Armiento

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Abstract

Matrix metalloproteinase- (MMP-1), or interstitial collagenase, has been hypothesized to contribute to the progression of the human atherosclerotic lesions by digesting the fibrillar collagens of the neointimal ECM. The apoE knockout (apoE0) mouse model develops complex atherosclerotic lesions, but mice do not possess a homologue for MMP-1. To provide an in vivo evaluation of the role of MMP-1 in atherogenesis, we created a transgenic mouse model that expresses this enzyme specifically in the macrophage, under the control of the scavenger receptor A (SCAV) enhancer/promoter. The MMP-1 transgenic mice were crossed into the apoE0 background and fed an atherogenic diet for 16-25 weeks. Surprisingly, the transgenic mice demonstrated decreased lesion size compared with control littermates. The lesions of the transgenic animals were less extensive and immature, with fewer cellular layers and a diminished content of fibrillar collagen. There was no evidence of plaque rupture. Our data suggest that remodeling of the neointimal ECM by MMP-1 is beneficial in the progression of lesions.

Original languageEnglish
Pages (from-to)1227-1234
Number of pages8
JournalJournal of Clinical Investigation
Volume107
Issue number10
Publication statusPublished - 2001

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lemaître, V., O'Byrne, T. K., Borczuk, A. C., Okada, Y., Tall, A. R., & D'Armiento, J. (2001). ApoE knockout mice expressing human matrix metalloproteinase-1 in macrophages have less advanced atherosclerosis. Journal of Clinical Investigation, 107(10), 1227-1234.