title: Specific matrix metalloproteinases play different roles in intraplaque angiogenesis and plaque instability in rabbits.
abstract: BACKGROUND
  Ectopic angiogenesis within the intima and media is considered to be a hallmark of advanced vulnerable atherosclerotic lesions. Some studies have shown that specific matrix metalloproteinases (MMPs) might play different roles in angiogenesis. Therefore, we investigated the predominant effects of specific MMPs in intraplaque angiogenesis and plaque instability in a rabbit model of atherosclerosis.
  
  
  RESULTS
  New Zealand rabbits underwent balloon injury of the abdominal artery and ingestion of a high-cholesterol (1%) diet to establish an atherosclerotic animal model. At weeks 4, 6, 8, 10, and 12 after balloon injury, five rabbits were euthanized and the abdominal aorta was harvested. Blood lipid analysis, intravascular ultrasound imaging, pathologic and immunohistochemical expression studies, and western blotting were performed. From weeks 4 to 12, the expression of MMP-1, -2, -3, and -9 and vascular endothelial growth factor A (VEGF-A) increased with atherosclerotic plaque development in the abdominal aorta, while the expression of MMP-14 substantially decreased. The vulnerability index (VI) gradually increased over time. Intraplaque neovessels appeared at week 8. The microvessel density (MVD) was greater at week 12 than at week 8. The VI, MVD, and VEGF-A level were positively correlated with the MMP-1, -2,-3, and -9 levels within plaques. Negative correlations were noted between the MMP-14 level and the VI, MVD, and VEGF-A level.
  
  
  CONCLUSIONS
  Upregulation of MMP-1, -2, -3, and -9 and downregulation of MMP-14 may contribute to intraplaque angiogenesis and plaque instability at the advanced stage of atherosclerosis in rabbits.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Shandong University Qilu Hospital, Jinan, Shandong, China; Department of Traditional Chinese Medicine, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors.forename: Xiao Qiong
authors.initials: XQ
authors.lastname: Liu
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Traditional Chinese Medicine, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors.forename: Xiao Ting
authors.initials: XT
authors.lastname: Lu
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Shandong University Qilu Hospital, Jinan, Shandong, China; Department of Traditional Chinese Medicine, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors.forename: Wen Wu
authors.initials: WW
authors.lastname: Bai
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Shandong University Qilu Hospital, Jinan, Shandong, China; Department of Traditional Chinese Medicine, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors.forename: Yuan Yuan
authors.initials: YY
authors.lastname: Sun
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Endodontics, Jinan Stomatologic Hospital, Jinan, Shandong, China.
authors.forename: Hong Mei
authors.initials: HM
authors.lastname: Liu
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Traditional Chinese Medicine, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors.forename: Yu Xia
authors.initials: YX
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000502:physiology*; D055806:Microvessels / Q000473:pathology / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000201:enzymology*; D058226:Plaque, Atherosclerotic / Q000201:enzymology* / Q000503:physiopathology; D011817:Rabbits
chemical_list: D020782:Matrix Metalloproteinases