title: Exercise training reduces neointimal growth and stabilizes vascular lesions developing after injury in apolipoprotein e-deficient mice.
abstract: BACKGROUND
  Population-based studies have shown that exercise reduces cardiovascular morbidity and mortality. However, it is unknown whether these effects are solely a result of risk factor modification or whether exercise directly affects the homeostasis of the vessel wall.
  
  
  RESULTS
  We subjected 19-week-old apolipoprotein E (apoE)-knockout mice (apoE(-/-); n=25) to a 6-week training program on a motorized treadmill. The control group consisted of 17 sedentary mice. After 3 weeks in the program, training and sedentary mice underwent carotid artery injury with ferric chloride. Training was then resumed for another 3 weeks. Exercise did not change body weight or lipid levels in apoE(-/-) mice but resulted in upregulated expression of nitric oxide synthase in the endothelium. Physical training did not significantly affect the thrombotic response to injury. However, morphometric analysis of vessels harvested 3 weeks after injury showed that neointima formation was reduced in the exercising group. This resulted in a lower intima/media ratio (0.29+/-0.03 versus 0.41+/-0.03 in sedentary mice; P=0.008) and less luminal stenosis (21+/-2.7% versus 33+/-2.3%; P=0.003). Importantly, exercise reduced the number of Mac-3-positive, oxidized LDL-containing macrophages in the vessel wall while increasing the content in collagen fibers (14.1+/-0.9% versus 4.8+/-0.8%; P<0.001). Plasminogen activator inhibitor-1, tissue factor, and fibrinogen were all significantly reduced in the lesions of trained mice.
  
  
  CONCLUSIONS
  In the apoE(-/-) mouse, exercise training reduces neointimal growth and stabilizes vascular lesions after injury. These effects appear to be at least partly independent of changes in lipid levels or the initial thrombotic response to injury.
authors.affiliation: Georg August University of Goettingen, Department of Cardiology and Pulmonary Medicine, Robert-Koch-Strasse 40, D-37075 Goettingen, Germany.
authors.forename: Marianne
authors.initials: M
authors.lastname: Pynn
authors.forename: Katrin
authors.initials: K
authors.lastname: Schäfer
authors.forename: Stavros
authors.initials: S
authors.lastname: Konstantinides
authors.forename: Martin
authors.initials: M
authors.lastname: Halle
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D002340:Carotid Artery Diseases / Q000209:etiology / Q000473:pathology / Q000628:therapy; D016893:Carotid Stenosis / Q000517:prevention & control; D002455:Cell Division; D005081:Exercise Therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010805:Physical Conditioning, Animal; D013927:Thrombosis / Q000209:etiology
chemical_list: D001057:Apolipoproteins E; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse