title: A new murine model of stress-induced complex atherosclerotic lesions.
abstract: The primary purpose of this investigation was to determine whether ApoE(-/-) mice, when subjected to chronic stress, exhibit lesions characteristic of human vulnerable plaque and, if so, to determine the time course of such changes. We found that the lesions were remarkably similar to human vulnerable plaque, and that the time course of lesion progression raised interesting insights into the process of plaque development. Lard-fed mixed-background ApoE(-/-) mice exposed to chronic stress develop lesions with large necrotic core, thin fibrous cap and a high degree of inflammation. Neovascularization and intraplaque hemorrhage are observed in over 80% of stressed animals at 20 weeks of age. Previously described models report a prevalence of only 13% for neovascularization observed at a much later time point, between 36 and 60 weeks of age. Thus, our new stress-induced model of advanced atherosclerotic plaque provides an improvement over what is currently available. This model offers a tool to further investigate progression of plaque phenotype to a more vulnerable phenotype in humans. Our findings also suggest a possible use of this stress-induced model to determine whether therapeutic interventions have effects not only on plaque burden, but also, and importantly, on plaque vulnerability.
authors: Cardiovascular Research Institute, MedStar Health Research Institute, 108 Irving Street, NW Washington, DC 20010, USA.
authors: Amir H
authors: AH
authors: Najafi
authors: Nima
authors: N
authors: Aghili
authors: Justin U
authors: JU
authors: Tilan
authors: James A
authors: JA
authors: Andrews
authors: XinZhi
authors: X
authors: Peng
authors: Roberta M
authors: RM
authors: Lassance-Soares
authors: Subeena
authors: S
authors: Sood
authors: Lee O
authors: LO
authors: Alderman
authors: Ken
authors: K
authors: Abe
authors: Lijun
authors: L
authors: Li
authors: Frank D
authors: FD
authors: Kolodgie
authors: Renu
authors: R
authors: Virmani
authors: Zofia
authors: Z
authors: Zukowska
authors: Stephen E
authors: SE
authors: Epstein
authors: Mary Susan
authors: MS
authors: Burnett
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000150:complications / Q000209:etiology* / Q000473:pathology*; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D023921:Coronary Stenosis / Q000150:complications / Q000473:pathology; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D006470:Hemorrhage / Q000150:complications / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D009389:Neovascularization, Pathologic / Q000150:complications / Q000473:pathology; D009478:Neuropeptide Y / Q000097:blood; D058226:Plaque, Atherosclerotic / Q000150:complications / Q000209:etiology* / Q000473:pathology*; D013315:Stress, Psychological / Q000097:blood / Q000150:complications*
chemical_list: D009478:Neuropeptide Y; D002784:Cholesterol; D003345:Corticosterone