BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is involved in atherosclerosis and elevated MMP-9 activity has been found in unstable plaques, suggesting a crucial role in plaque rupture. This study aims to assess the effect of MMP-9 on plaque stability in apolipoprotein E-deficient mice at different stages of plaque progression. METHODS AND RESULTS: Atherosclerotic lesions were elicited in carotid arteries by perivascular collar placement. MMP-9 overexpression in intermediate or advanced plaques was effected by intraluminal incubation with an adenovirus (Ad.MMP-9). A subset was coincubated with Ad.TIMP-1. Mock virus served as a control. Plaques were analyzed histologically. In intermediate lesions, MMP-9 overexpression induced outward remodeling, as shown by a 30% increase in media size (p=0.03). In both intermediate and advanced lesions, prevalence of vulnerable plaque morphology tended to be increased. Half of MMP-9-treated lesions displayed intraplaque hemorrhage, whereas in controls and the Ad.MMP-9/Ad.TIMP-1 group this was 8% and 16%, respectively (p=0.007). Colocalization with neovessels may point to neo-angiogenesis as a source for intraplaque hemorrhage. CONCLUSIONS: These data show a differential effect of MMP-9 at various stages of plaque progression and suggest that lesion-targeted MMP-9 inhibition might be a valuable therapeutic modality in stabilizing advanced plaques, but not at earlier stages of lesion progression.
BACKGROUND:Matrix metalloproteinase-9 (MMP-9) is involved in atherosclerosis and elevated MMP-9 activity has been found in unstable plaques, suggesting a crucial role in plaque rupture. This study aims to assess the effect of MMP-9 on plaque stability in apolipoprotein E-deficientmice at different stages of plaque progression. METHODS AND RESULTS:Atherosclerotic lesions were elicited in carotid arteries by perivascular collar placement. MMP-9 overexpression in intermediate or advanced plaques was effected by intraluminal incubation with an adenovirus (Ad.MMP-9). A subset was coincubated with Ad.TIMP-1. Mock virus served as a control. Plaques were analyzed histologically. In intermediate lesions, MMP-9 overexpression induced outward remodeling, as shown by a 30% increase in media size (p=0.03). In both intermediate and advanced lesions, prevalence of vulnerable plaque morphology tended to be increased. Half of MMP-9-treated lesions displayed intraplaque hemorrhage, whereas in controls and the Ad.MMP-9/Ad.TIMP-1 group this was 8% and 16%, respectively (p=0.007). Colocalization with neovessels may point to neo-angiogenesis as a source for intraplaque hemorrhage. CONCLUSIONS: These data show a differential effect of MMP-9 at various stages of plaque progression and suggest that lesion-targeted MMP-9 inhibition might be a valuable therapeutic modality in stabilizing advanced plaques, but not at earlier stages of lesion progression.
Authors: Veronica Herías; Erik A L Biessen; Cora Beckers; Dianne Delsing; Mengyang Liao; Mat J Daemen; Christine C T N Pham; Sylvia Heeneman Journal: Arterioscler Thromb Vasc Biol Date: 2014-11-13 Impact factor: 8.311
Authors: Shann S Yu; Ryan A Ortega; Brendan W Reagan; John A McPherson; Hak-Joon Sung; Todd D Giorgio Journal: Wiley Interdiscip Rev Nanomed Nanobiotechnol Date: 2011-08-10
Authors: Jan H von der Thüsen; Keren S Borensztajn; Silvia Moimas; Sandra van Heiningen; Peter Teeling; Theo J C van Berkel; Erik A L Biessen Journal: Am J Pathol Date: 2011-02 Impact factor: 4.307
Authors: Amie K Lund; JoAnn Lucero; Melissa Harman; Michael C Madden; Jacob D McDonald; Jean Clare Seagrave; Matthew J Campen Journal: Am J Respir Crit Care Med Date: 2011-04-14 Impact factor: 21.405