Compensatory vascular remodeling during atherosclerotic lesion growth depends on matrix metalloproteinase-9 activity.

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 (P<0.0001) by 14 days. At the same time, the net lesion area occupied by macrophages was similar. Statistical analysis indicated that the overall expansion of the artery was 2.5-fold less sensitive to macrophage content in DKO compared with apoE-/- mice. No compensatory increase in other gelatinolytic activities was detected in the DKO.

CONCLUSIONS: MMP-9 deficiency significantly impaired compensatory vessel enlargement during carotid artery lesion development in the apoE-/- mouse, without altering macrophage content of lesions.