title: Rosiglitazone modulates collagen deposition and metabolism in atherosclerotic plaques of fat-fed ApoE-knockout mice.
abstract: Abnormal collagen deposition, as well as collagen metabolism, plays a crucial role in the formation and progression of vulnerable atherosclerotic plaques (VAPs), which are susceptible to rupture. According to our previous findings, rosiglitazone, a thiazolidinedione, can promote the stability of atherosclerotic plaques in fat-fed ApoE-knockout mice; however, it is unknown whether it can modulate collagen deposition and metabolism in VAPs. The present study was designed to determine the effect of rosiglitazone on collagen deposition and metabolism in the plaques of fat-fed ApoE-knockout mice. Following 13 weeks of the high-fat diet, the mice were randomized into three groups (10 mice/group) and intragastrically administered rosiglitazone, simvastatin and distilled water, respectively, for a further 13 weeks. The category of the collagen present in the plaques was evaluated using the picro-Sirius red polarization method. Additionally, the protein expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the plaques was determined using immunohistochemistry. The results showed that rosiglitazone reduced the lipid to collagen and type III to type I collagen ratios in the plaques, and these reductions were correlated with the reduction in the plaque MMP-9 to TIMP-1 ratio. These results suggest that rosiglitazone can modulate collagen deposition and metabolism and promote the stabilization of VAPs.
authors.affiliation: Beijing Institute of Traditional Chinese Medicine, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing 100010, P.R. China.
authors.forename: Mingxue
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Cardiovascular Medicine, Xiyuan Hospital, Academy of Chinese Medical Sciences, Beijing 100091, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.affiliation: Beijing Institute of Traditional Chinese Medicine, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing 100010, P.R. China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Medicine, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing 100010, P.R. China.
authors.forename: Hongxu
authors.initials: H
authors.lastname: Liu
keywords: atherosclerosis; collagen deposition and metabolism; plaque stability; rosiglitazone