title: Angiotensin II induces histomorphologic features of unstable plaque in a murine model of accelerated atherosclerosis.
abstract: BACKGROUND
  We explored the role of angiotensin II in determining the histomorphometric features of plaque stability in apolipoprotein E-deficient mice submitted to ligation of the carotid artery.
  
  
  METHODS
  Six-month-old apolipoprotein E-deficient mice underwent ligation of the common left carotid artery and were immediately assigned to receive either angiotensin II (1.4 mg . kg(-1) . d(-1) subcutaneously) or vehicle (phosphate-buffered saline; control) via a subcutaneous osmotic minipump for 4 weeks.
  
  
  RESULTS
  Ligated arteries from control animals developed intimal lesions composed of macrophage foam cell plaques, which accumulated adjacent to the internal elastic lamina and were surrounded by a fibromuscular layer. Angiotensin II-treated mice had a greater intimal area (threefold), which was accompanied by a fivefold increase in the foam cell area. Lesions from angiotensin II-treated mice also displayed complex morphology characterized by intralesional neovasculature and hemorrhage. The content of active matrix metalloproteinase 2, mainly colocalized with macrophage foam cells, and the production of the inflammatory mediators monocyte chemoattractant protein 1 and vascular cell adhesion molecule 1 were also increased by angiotensin II treatment. Although angiotensin II induced vessel expansion and lumen loss to a similar extent, only vessel enlargement correlated with intimal area.
  
  
  CONCLUSIONS
  Taken together, this study's results support a role of angiotensin II in plaque vulnerability by promoting intraplaque neovascularization/hemorrhage, inflammation, and expansive remodeling.
authors.affiliation: Department of Pharmacology, Berlex Biosciences, Richmond, CA, USA. valdeci_dacunha@yahoo.com
authors.forename: Valdeci
authors.initials: V
authors.lastname: da Cunha
authors.forename: Baby
authors.initials: B
authors.lastname: Martin-McNulty
authors.forename: Jon
authors.initials: J
authors.lastname: Vincelette
authors.forename: David F
authors.initials: DF
authors.lastname: Choy
authors.forename: We-Wei
authors.initials: WW
authors.lastname: Li
authors.forename: Miriam
authors.initials: M
authors.lastname: Schroeder
authors.forename: Mithra
authors.initials: M
authors.lastname: Mahmoudi
authors.forename: Meredith
authors.initials: M
authors.lastname: Halks-Miller
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Wilson
authors.forename: Ronald
authors.initials: R
authors.lastname: Vergona
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sullivan
authors.forename: Yi-Xin Jim
authors.initials: YX
authors.lastname: Wang
mesh_terms: D000804:Angiotensin II; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology* / Q000601:surgery; D002340:Carotid Artery Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D005487:Foam Cells / Q000187:drug effects / Q000473:pathology; D007150:Immunohistochemistry; D008026:Ligation; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D019010:Vascular Cell Adhesion Molecule-1; D000804:Angiotensin II; D020778:Matrix Metalloproteinase 2