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Title: Loss of ADAMTS4 reduces high fat diet-induced atherosclerosis and enhances plaque stability in ApoE-/- mice
Authors: Kumar S. 
Chen M. 
Li Y.
Wong F.H.S. 
Thiam C.W. 
Hossain M.Z. 
Poh K.K. 
Hirohata S.
Ogawa H.
Angeli V. 
Ge R. 
Keywords: Adamts4 protein, mouse
aggrecanase 1
apolipoprotein E
atherosclerotic plaque
knockout mouse
lipid diet
ADAMTS4 Protein
Apolipoproteins E
Diet, High-Fat
Mice, Knockout
Plaque, Atherosclerotic
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: Kumar S., Chen M., Li Y., Wong F.H.S., Thiam C.W., Hossain M.Z., Poh K.K., Hirohata S., Ogawa H., Angeli V., Ge R. (2016). Loss of ADAMTS4 reduces high fat diet-induced atherosclerosis and enhances plaque stability in ApoE-/- mice. Scientific Reports 6 : 31130. ScholarBank@NUS Repository.
Abstract: Atherosclerosis is a chronic inflammatory disease characterized by formation of lipid-rich plaques on the inner walls of arteries. ADAMTS4 (a disintegrin-like and metalloproteinase with thrombospondin motifs-4) is a secreted proteinase that regulates versican turnover in the arterial wall and atherosclerotic plaques. Recent reports indicated elevated ADAMTS4 level in human atherosclerotic plaques and in the plasma of acute coronary syndrome patients. Nevertheless, whether increased ADAMTS4 is a consequence of atherosclerosis or ADAMTS4 has a causal role in atherogenesis remains unknown. In this work, we investigated the role of ADAMTS4 in diet induced atherosclerosis using apolipoprotein E deficient (ApoE-/-) and Adamts4 knockout mice. We show that ADAMTS4 expression increases in plaques as atherosclerosis progresses in ApoE-/- mice. ApoE-/- Adamts4-/- double knockout mice presented a significant reduction in plaque burden at 18 weeks of age. Loss of ADAMTS4 lead to a more stable plaque phenotype with a significantly reduced plaque vulnerability index characterized by reduced lipid content and macrophages accompanied with a significant increase in smooth muscle cells, collagen deposition and fibrotic cap thickness. The reduced atherosclerosis is accompanied by an altered plasma inflammatory cytokine profile. These results demonstrate for the first time that ADAMTS4 contributes to diet induced atherosclerosis in ApoE-/- mice.
Source Title: Scientific Reports
ISSN: 20452322
DOI: 10.1038/srep31130
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