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 language | English |
|---|---|
| Pages (from-to) | 107-112 |
| Number of pages | 6 |
| Journal | Atherosclerosis |
| Volume | 205 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2009 Jul |
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Keywords
- Collagen
- Matrix metalloproteinase
- Mouse model of atherosclerosis
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Transgenic expression of matrix metalloproteinase-9 modulates collagen deposition in a mouse model of atherosclerosis. / Lemaître, Vincent; Kim, Henry E.; Forney-Prescott, Margaret; Okada, Yasunori; D'Armiento, Jeanine.
In: Atherosclerosis, Vol. 205, No. 1, 07.2009, p. 107-112.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Transgenic expression of matrix metalloproteinase-9 modulates collagen deposition in a mouse model of atherosclerosis
AU - Lemaître, Vincent
AU - Kim, Henry E.
AU - Forney-Prescott, Margaret
AU - Okada, Yasunori
AU - D'Armiento, Jeanine
PY - 2009/7
Y1 - 2009/7
N2 - 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.
AB - 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.
KW - Collagen
KW - Matrix metalloproteinase
KW - Mouse model of atherosclerosis
UR - http://www.scopus.com/inward/record.url?scp=67349160215&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67349160215&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2008.11.030
DO - 10.1016/j.atherosclerosis.2008.11.030
M3 - Article
C2 - 19144335
AN - SCOPUS:67349160215
VL - 205
SP - 107
EP - 112
JO - Atherosclerosis
JF - Atherosclerosis
SN - 0021-9150
IS - 1
ER -