Key Points
- To assess the stage-dependent effects of matrix metalloproteinase-9 (MMP-9) overexpression on plaque stability and remodeling in apolipoprotein E-deficient mice.
- Induced carotid atherosclerotic lesions in apolipoprotein E-deficient mice using perivascular collar placement.
- Overexpressed MMP-9 intraluminally in intermediate or advanced plaques via an adenoviral vector (Ad.MMP-9), with subsets receiving Ad.TIMP-1 co-incubation or mock virus controls.
- Conducted histological analyses to evaluate plaque morphology, vessel remodeling, and bleeding within lesions.
- MMP-9 overexpression in intermediate lesions caused outward vascular remodeling, evidenced by a 30% increase in media size (p=0.03).
- Advanced lesions overexpressing MMP-9 showed intraplaque hemorrhage in 50% of cases compared to 8% in controls and 16% in the Ad.MMP-9/Ad.TIMP-1 group (p=0.007).
- Areas of intraplaque hemorrhage colocalized with neovessels, indicating neo-angiogenesis as a likely source of bleeding.
Structured PICO
Does MMP-9 overexpression affect plaque stability and intraplaque hemorrhage in apolipoprotein E-deficient mice at different stages of plaque progression?
PPopulationApolipoprotein E-deficient mice with atherosclerotic lesions elicited in carotid arteries by perivascular collar placement
IInterventionIntraluminal incubation with an adenovirus (Ad.MMP-9) to overexpress MMP-9 in intermediate or advanced plaques
CComparatorMock virus control and a subset coincubated with Ad.TIMP-1
OOutcomePlaque stability and morphology assessed histologically (including intraplaque hemorrhage and outward remodeling)surrogate
MMP-9 overexpression promotes intraplaque hemorrhage in advanced atherosclerotic lesions but induces outward remodeling in intermediate lesions, suggesting stage-specific effects.