This Article Full Text Full Text (PDF) All Versions of this Article: 109/3/386    most recent 01.CIR.0000109500.03050.7Cv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pynn, M. Articles by Halle, M. Search for Related Content PubMed PubMed Citation Articles by Pynn, M. Articles by Halle, M. Pubmed/NCBI databases Substance via MeSH Related Collections Animal models of human disease Pathophysiology Genetically altered mice Exercise/exercise testing/rehabilitation

(Circulation. 2004;109:386-392.)
© 2004 American Heart Association, Inc.

Basic Science Reports

Exercise Training Reduces Neointimal Growth and Stabilizes Vascular Lesions Developing After Injury in Apolipoprotein E–Deficient Mice

From the Georg August University of Goettingen, Department of Cardiology and Pulmonary Medicine, Goettingen, Germany. Dr Halle is now at the Technical University, Department of Internal Medicine, Division of Prevention, Rehabilitation, and Sports Medicine, Munich, Germany.

Correspondence to Stavros Konstantinides, MD, Georg August University of Goettingen, Department of Cardiology and Pulmonary Medicine, Robert-Koch-Straße 40, D-37075 Goettingen, Germany. E-mail skonstan{at}med.uni-goettingen.de

Received June 20, 2003; revision received September 25, 2003; accepted September 25, 2003.

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.

Methods and 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.

Key Words: exercise • atherosclerosis • plaque • cholesterol • thrombosis

This article has been cited by other articles:

				B. S. Fleenor and D. K. Bowles Exercise training decreases the size and alters the composition of the neointima in a porcine model of percutaneous transluminal coronary angioplasty (PTCA) J Appl Physiol, September 1, 2009; 107(3): 937 - 945. [Abstract] [Full Text] [PDF]

				T.-a. Okabe, K. Shimada, M. Hattori, T. Murayama, M. Yokode, T. Kita, and C. Kishimoto Swimming reduces the severity of atherosclerosis in apolipoprotein E deficient mice by antioxidant effects Cardiovasc Res, June 1, 2007; 74(3): 537 - 545. [Abstract] [Full Text] [PDF]

				U. Hagg, M. E. Johansson, J. Gronros, A. S. Naylor, I. H. Jonsdottir, G. Bergstrom, P.-A. Svensson, and L.-m. Gan Gene expression profile and aortic vessel distensibility in voluntarily exercised spontaneously hypertensive rats: potential role of heat shock proteins Physiol Genomics, August 11, 2005; 22(3): 319 - 326. [Abstract] [Full Text] [PDF]

				L. R. Leon Jr, N. Labropoulos, P. Lebda, and P. G. Kalman The Vascular Surgeon's Role in Risk Factor Modification: Results of a Survey Perspectives in Vascular Surgery and Endovascular Therapy, June 1, 2005; 17(2): 145 - 153. [Abstract] [PDF]