Selective inhibition of matrix metalloproteinase-13 increases collagen content of established mouse atherosclerosis.

ABSTRACT:

Objective

Evidence has linked collagen loss with the onset of acute coronary events. This study tested the hypothesis that selective matrix metalloproteinase-13 (MMP-13) collagenase inhibition increases collagen content in already established and nascent mouse atheromas.

Methods and results

In vitro and in situ experiments documented the selectivity and efficacy of an orally available MMP-13 inhibitor (MMP13i-A). In vivo observations monitored macrophage accumulation and MMP-13 activity using molecular imaging. After 10 weeks of MMP13i-A treatment, apolipoprotein E-deficient mice with evolving or established lesions exhibited reduced MMP-13 activity without affecting macrophage content, measured either by intravital microscopy or fluorescence reflectance imaging. Histologica

SUBMITTER: Quillard T 

PROVIDER: S-EPMC3200308 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature