title: Preventive and therapeutic moderate aerobic exercise programs convert atherosclerotic plaques into a more stable phenotype.
abstract: The mechanisms by which exercise affects atherosclerotic plaque stability remain incompletely understood. We evaluated the effects of two training protocols on both atherosclerotic plaque structure and the signaling pathways involved in plaque rupture.
  
  
  METHODS
  Male low-density lipoprotein (LDL) receptor knockout mice were fed a high-fat, high-cholesterol diet (HFD). One group was subjected to moderate exercise using a treadmill for 14weeks (preventive protocol). The other group started an exercise regimen after 16weeks of the HFD (therapeutic group). Atherosclerotic plaques within the aorta were evaluated for lipid and collagen contents, as well as for inflammatory markers. Plasma cholesterol and cytokine levels were also determined.
  
  
  RESULTS
  The mice receiving a HFD developed hypercholesterolemia and atherosclerotic plaques within the aorta. The aortas from the animals in the preventive protocol exhibited smaller lipid cores and higher collagen content. These animals also exhibited lower CD40 expression within the plaques. The aortas of the mice in the therapeutic group exhibited higher collagen content, but no differences in either lipid core size or plaque size were noted. No differences in blood pressure, plasma cholesterol, cytokine levels, plaque size or metalloproteinase 9 expression were observed in the trained animals compared with the sedentary animals.
  
  
  CONCLUSIONS
  Moderate aerobic exercise modified atherosclerotic plaque characteristics and converted the plaques into a more stable phenotype, increasing the collagen content in response to both exercise programs. Furthermore, moderate aerobic exercise reduced the animals' fat content and decreased the activity of the CD40-CD40L signaling pathway in the preventive group.
authors.affiliation: Emergency Medicine Department (LIM-51), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Themis M
authors.initials: TM
authors.lastname: Cardinot
authors.affiliation: Emergency Medicine Department (LIM-51), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. Electronic address: thais@emercli.fm.usp.br.
authors.forename: Thais M
authors.initials: TM
authors.lastname: Lima
authors.affiliation: Emergency Medicine Department (LIM-51), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Ana I S
authors.initials: AI
authors.lastname: Moretti
authors.affiliation: Emergency Medicine Department (LIM-51), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Marcia K
authors.initials: MK
authors.lastname: Koike
authors.affiliation: Lipids Laboratory (LIM-10), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Valeria S
authors.initials: VS
authors.lastname: Nunes
authors.affiliation: Lipids Laboratory (LIM-10), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Cazita
authors.affiliation: Department of Physiology and Biophysics, Institute of Biology, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Marta H
authors.initials: MH
authors.lastname: Krieger
authors.affiliation: School of Physical Education and Sports, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Brum
authors.affiliation: Emergency Medicine Department (LIM-51), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Heraldo P
authors.initials: HP
authors.lastname: Souza
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010805:Physical Conditioning, Animal; D058226:Plaque, Atherosclerotic / Q000503:physiopathology*
keywords: Aerobic exercise; Atherosclerosis; High fat diet; Plaque stability