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MMP-2 and MMP-9 are prominent matrix metalloproteinases during atherosclerosis development in the LdlrApob100/100 mouse
Karolinska Institute, Solna, Stockholm, Sweden.
Karolinska Institute, Solna, Stockholm, Sweden.
Karolinska Institute, Solna, Stockholm, Sweden.
Karolinska Institute, Solna, Stockholm, Sweden.
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2011 (English)In: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 28, no 2, 247-253 p.Article in journal (Refereed) Published
Abstract [en]

Matrix-degrading proteases capable of degrading components of the extracellular matrix may play an important role in development and progression of atherosclerotic lesions. In the present study, we used the Ldlr(-/-)Apob(100/100) mouse model, which has a plasma lipoprotein profile similar to that of humans with atherosclerosis, to study the expression of matrix metalloproteinases (MMPs) during early stages of atherosclerosis development. We analyzed the expression of 11 proteases and three protease inhibitors in 5- to 40-week-old Ldlr(-/-)Apob(100/100) mice. Expression and activity of MMP-2 and MMP-9 was increased in advanced atherosclerotic lesions followed by macrophage infiltration as shown by real-time PCR, gel-based and in situ zymography and immunohistochemistry. Expression of other investigated MMPs did not increase during disease progression. However, the mRNA expression of MMP-8 and MMP-13 was down-regulated, which could explain the relatively high amount of collagen observed in the vessels in this model. In conclusion, low proteolytic expression at early stages of atherogenesis and a limited repertoire of proteolytic enzymes were associated with the progression of atherosclerosis in Ldlr(-/-)Apob(100/100) mice. The study suggests that MMP-2 and MMP-9 are the main proteases involved in atherogenesis in this mouse model.

Place, publisher, year, edition, pages
Spandidos Publications , 2011. Vol. 28, no 2, 247-253 p.
Keyword [en]
protease; apolipoprotein B 100; extracellular matrix; atherosclerosis
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-100334DOI: 10.3892/ijmm.2011.693ISI: 000292715200014PubMedID: 21567073OAI: diva2:661709
Available from: 2013-11-04 Created: 2013-11-04 Last updated: 2013-11-18Bibliographically approved

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