title: A role of matrix metalloproteinase-8 in atherosclerosis.
abstract: BACKGROUND
  Atherosclerotic lesions express matrix metalloproteinase (MMP)8, which possesses proteolytic activity on matrix proteins particularly fibrillar collagens and on nonmatrix proteins such as angiotensin (Ang) I.
  
  
  OBJECTIVE
  We studied whether MMP8 plays a role in atherogenesis.
  
  
  RESULTS
  In atherosclerosis-prone apolipoprotein E-deficient mice, inactivating MMP8 resulted in a substantial reduction in atherosclerotic lesion formation. Immunohistochemical examinations showed that atherosclerotic lesions in MMP8-deficient mice had significantly fewer macrophages but increased collagen content. In line with results of in vitro assays showing that Ang I cleavage by MMP8 generated Ang II, MMP8 knockout mice had lower Ang II levels and lower blood pressure. In addition, we found that products of Ang I cleavage by MMP8 increased vascular cell adhesion molecule (VCAM)-1 expression and that MMP8-deficient mice had reduced VCAM-1 expression in atherosclerotic lesions. Intravital microscopy analysis showed that leukocyte rolling and adhesion on vascular endothelium was reduced in MMP8 knockout mice. Furthermore, we detected an association between MMP8 gene variation and extent of coronary atherosclerosis in patients with coronary artery disease. A relationship among MMP8 gene variation, plasma VCAM-1 level, and atherosclerosis progression was also observed in a population-based, prospective study.
  
  
  CONCLUSIONS
  These results indicate that MMP8 is an important player in atherosclerosis.
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, United Kingdom.
authors.forename: Ross C
authors.initials: RC
authors.lastname: Laxton
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Hu
authors.forename: Johan
authors.initials: J
authors.lastname: Duchene
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Kit-Yi
authors.initials: KY
authors.lastname: Leung
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Xiao
authors.forename: Ramona S
authors.initials: RS
authors.lastname: Scotland
authors.forename: Conrad P
authors.initials: CP
authors.lastname: Hodgkinson
authors.forename: Katherine
authors.initials: K
authors.lastname: Smith
authors.forename: Johann
authors.initials: J
authors.lastname: Willeit
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Otín
authors.forename: Iain A
authors.initials: IA
authors.lastname: Simpson
authors.forename: Stefan
authors.initials: S
authors.lastname: Kiechl
authors.forename: Amrita
authors.initials: A
authors.lastname: Ahluwalia
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Xu
authors.forename: Shu
authors.initials: S
authors.lastname: Ye
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001018:Aortic Diseases / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control; D001794:Blood Pressure; D002340:Carotid Artery Diseases / Q000201:enzymology* / Q000235:genetics / Q000517:prevention & control; D003094:Collagen / Q000378:metabolism; D023921:Coronary Stenosis / Q000201:enzymology* / Q000235:genetics / Q000517:prevention & control; D004195:Disease Models, Animal; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000378:metabolism; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D036904:Leukocyte Rolling; D008264:Macrophages / Q000378:metabolism; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012720:Severity of Illness Index; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D019010:Vascular Cell Adhesion Molecule-1; D000804:Angiotensin II; D003094:Collagen; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8