Transgenic expression of matrix metalloproteinase-9 modulates collagen deposition in a mouse model of atherosclerosis

Vincent Lemaître, Henry E. Kim, Margaret Forney-Prescott, Yasunori Okada, Jeanine D'Armiento

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Matrix metalloproteinase-9 (MMP-9) has been proposed to be an important modulator of atherosclerotic plaque vulnerability. We generated a transgenic (tg) model expressing human proMMP-9 in macrophages, using the scavenger receptor enhancer/promoter A. This model was crossed into the double Apoe/Timp-1 knockout background. After 16 weeks of a high-fat diet, there were no significant changes in plaque size in the proximal aortas between the four groups of the study population (Apoe-/-, Apoe-/-/MMP-9tg, Apoe-/-/Timp-1-/-, and Apoe-/-/MMP-9tg/Timp-1-/-), and, in the Timp-1 knockout background, MMP-9 transgenic mice and control littermates had similar micro-aneurysm formation. However, lesions in Apoe-/-/MMP-9tg/Timp-1-/- mice contained significantly more collagen compared to the three other groups (P < 0.005). Culture supernatants from elicited Apoe-/-/MMP-9tg/Timp-1-/- macrophages contained higher levels of active TGF-β than the three other groups (P < 0.05), suggesting that augmented collagen deposition resulted from an increase in TGF-β activation due to transgenic MMP-9 in the Timp-1-/- background. This study indicates that, in human atherosclerosis, increased MMP-9 activity could up-regulate collagen deposition, possibly through TGF-β activation.

Original languageEnglish
Pages (from-to)107-112
Number of pages6
JournalAtherosclerosis
Volume205
Issue number1
DOIs
Publication statusPublished - 2009 Jul 1

Keywords

  • Collagen
  • Matrix metalloproteinase
  • Mouse model of atherosclerosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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