title: Marked acceleration of atherosclerosis after Lactobacillus casei-induced coronary arteritis in a mouse model of Kawasaki disease.
abstract: OBJECTIVE
  The purpose of this study was to investigate whether Lactobacillus casei cell wall extract-induced Kawasaki disease (KD) accelerates atherosclerosis in hypercholesterolemic mice.  Method and Results- Apolipoprotein E knockout or low-density lipoprotein receptor knockout mice were injected with Lactobacillus casei cell wall extract (KD mice) or PBS, fed high-fat diet for 8 weeks, and atherosclerotic lesions in aortic sinuses, arch (AC), and whole aorta were assessed. KD mice had larger, more complex aortic lesions with abundant collagen, and both extracellular and intracellular lipid and foam cells, compared with lesions in control mice despite similar cholesterol levels. Both apolipoprotein E knockout KD and low-density lipoprotein receptor knockout KD mice showed dramatic acceleration in atherosclerosis versus controls, with increases in en face aortic atherosclerosis and plaque size in both the aortic sinuses and AC plaques. Accelerated atherosclerosis was associated with increased circulating interleukin-12p40, interferon-γ, tumor necrosis factor-α, and increased macrophage, dendritic cell, and T-cell recruitment in lesions. Furthermore, daily injections of the interleukin-1Ra, which inhibits Lactobacillus casei cell wall extract-induced KD vasculitis, prevented the acceleration of atherosclerosis.
  
  
  CONCLUSIONS
  Our results suggest an important pathophysiologic link between coronary arteritis/vasculitis in the KD mouse model and subsequent atherosclerotic acceleration, supporting the concept that a similar relation may also be present in KD patients. These results also suggest that KD in childhood may predispose to accelerated and early atherosclerosis as adults.
authors.affiliation: David Geffen School of Medicine at the University of California, Division of Pediatric Infectious Diseases and Immunology, Burns and Allen Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048, USA.
authors.forename: Shuang
authors.initials: S
authors.lastname: Chen
authors.forename: Youngho
authors.initials: Y
authors.lastname: Lee
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Crother
authors.forename: Michael
authors.initials: M
authors.lastname: Fishbein
authors.forename: Wenxuan
authors.initials: W
authors.lastname: Zhang
authors.forename: Atilla
authors.initials: A
authors.lastname: Yilmaz
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shimada
authors.forename: Danica J
authors.initials: DJ
authors.lastname: Schulte
authors.forename: Thomas J A
authors.initials: TJ
authors.lastname: Lehman
authors.forename: Prediman K
authors.initials: PK
authors.lastname: Shah
authors.forename: Moshe
authors.initials: M
authors.lastname: Arditi
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology; D001167:Arteritis / Q000150:complications*; D050197:Atherosclerosis / Q000188:drug therapy / Q000209:etiology*; D003324:Coronary Artery Disease / Q000150:complications*; D003713:Dendritic Cells / Q000502:physiology; D004195:Disease Models, Animal; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D007780:Lacticaseibacillus casei; D051379:Mice; D008810:Mice, Inbred C57BL; D009080:Mucocutaneous Lymph Node Syndrome / Q000150:complications*; D058226:Plaque, Atherosclerotic / Q000209:etiology; D011973:Receptors, LDL / Q000502:physiology
chemical_list: D001057:Apolipoproteins E; D053590:Interleukin 1 Receptor Antagonist Protein; D011973:Receptors, LDL