Long-Term Exercise Stabilizes Atherosclerotic Plaque in ApoE Knockout Mice

PELLEGRIN, MAXIME1,2,3; MIGUET-ALFONSI, CAROLE1,2; BOUZOURENE, KARIMA3; AUBERT, JEAN-FRANÇOIS3; DECKERT, VALÉRIE4; BERTHELOT, ALAIN1; MAZZOLAI, LUCIA3; LAURANT, PASCAL1,2

Medicine & Science in Sports & Exercise: December 2009 - Volume 41 - Issue 12 - pp 2128-2135
doi: 10.1249/MSS.0b013e3181a8d530
Basic Sciences

Purpose: Exercise is known to reduce cardiovascular mortality. However, the precise mechanisms are still unknown. Because atherosclerotic plaque destabilization and rupture leads to dramatic cardiovascular events, stabilization of plaque might be regarded as an important goal of an exercise preventive therapy. The present study examined the plaque-stabilizing effect of long-term exercise in experimental atherosclerosis using apolipoprotein E-deficient mice (ApoE−/−).

Methods: ApoE−/− mice were subjected to 6 months of swimming exercise. A group of sedentary animals were used as controls. Morphometry and characteristics of atherosclerotic plaque stability were assessed in aortic sinus by immunohistochemistry. Aortic levels of total protein kinase Akt (protein kinase B), phosphorylated Akt at Ser473 (p-Akt), total endothelial nitric oxide synthase (eNOS), and phosphorylated eNOS at Ser1177 (p-eNOS) were assessed by Western blotting.

Results: Exercised mice developed a more stable plaque phenotype as shown by decreased macrophage and increased smooth muscle cell content. Protein expressions of Akt, p-Akt, eNOS, and p-eNOS were not modulated by exercise.

Conclusions: Long-term exercise promotes plaque stability in ApoE−/− mice. The Akt-mediated eNOS phosphorylation pathway seems not to be the primary molecular mechanism.

1EA-4267/2SBP, University of Franche-Comté, Besançon, FRANCE; 2Exercise Prevention Innovation and Technico-Sporting Watching Department, Besançon, FRANCE; 3Service of Vascular Medicine, Department of Internal Medicine, Lausanne University Hospital, CHUV, Lausanne, SWITZERLAND; and 4INSERM U866, Faculty of Medicine, University of Bourgogne, Dijon, FRANCE

Address for correspondence: Maxime Pellegrin, Ph.D., Service of Vascular Medicine, CHUV, Av. Pierre Decker 5, 1011 Lausanne, Switzerland; E-mail: Maxime.Pellegrin@chuv.ch.

Submitted for publication December 2008.

Accepted for publication April 2009.

©2009The American College of Sports Medicine