Work

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

Year: 2001

Type: article

Abstract: Matrix metalloproteinase-1 (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 apolipoprotein E 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 extracellular matrix by MMP-1 is beneficial in the progression of lesions.

Source: Journal of Clinical Investigation

DOI: 10.1172/jci9626

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

Institutions: Columbia University, Keio University

Language: English

Topic: Atherosclerosis and Cardiovascular Diseases

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: American Heart Association, Pfizer, National Institutes of Health, National Heart, Lung, and Blood Institute