Compensatory Vascular Remodeling During Atherosclerotic Lesion Growth Depends on Matrix Metalloproteinase-9 Activity

Abstract

Objective—The compensatory arterial remodeling associated with atherosclerotic plaques is thought to rely on the activity of matrix metalloproteinases (MMP). To assess the role of MMP-9, we analyzed the effect of MMP-9 genetic deficiency on the development and remodeling of experimental atherosclerotic lesions induced in the apolipoprotein E (apoE) knockout (−/−) mouse model.Methods and Results—We analyzed remodeling parameters and cellular composition of experimental carotid artery atherosclerotic lesions in apoE−/− and apoE−/− MMP-9−/− double-knockout (DKO) mice at 0, 3, 7, and 14 days after induction by flow cessation. Morphometric image analysis of arterial tissue sections indicated that overall artery size, measured as area encompassed by the external elastic lamina, increased 3.1-fold in the apoE−/− mice but only 1.6-fold in the DKO mice (PConclusions—MMP-9 deficiency significantly impaired compensatory vessel enlargement during carotid artery lesion development in the apoE−/− mouse, without altering macrophage content of lesions.