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

研究成果: Article査読

163 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1227-1234
ページ数8
ジャーナルJournal of Clinical Investigation
107
10
DOI
出版ステータスPublished - 2001

ASJC Scopus subject areas

  • Medicine(all)

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