title: Running Exercise and Angiotensin II Type I Receptor Blocker Telmisartan Are Equally Effective in Preventing Angiotensin II-Mediated Vulnerable Atherosclerotic Lesions.
abstract: BACKGROUND
  The present study was conducted to directly compare the efficacy of running exercise and telmisartan treatment on angiotensin (Ang) II-mediated atherosclerosis and plaque vulnerability.
  
  
  METHODS
  Apolipoprotein E-deficient (ApoE-/-) mice with Ang II-mediated atherosclerosis (2-kidney, 1-clip [2K1C] renovascular hypertension model) were randomized into 3 groups: treadmill running exercise (RUN), telmisartan treatment (TEL), and sedentary untreated controls (SED) for 5 weeks. Atherosclerosis was assessed using histological and immunohistochemical analyses. Gene expression was determined by real-time reverse transcription polymerase chain reaction.
  
  
  RESULTS
  TEL but not RUN mice significantly decreased (50%) atherosclerotic lesion size compared to SED. RUN and TEL promoted plaque stabilization to a similar degree in ApoE-/-2K1C mice. However, plaque composition and vascular inflammatory markers were differently affected: RUN decreased plaque macrophage infiltration (35%), whereas TEL reduced lipid core size (88%); RUN significantly increased aortic peroxisome proliferator-activated receptor (PPAR)-α, -δ, and -γ expression, whereas TEL significantly modulated T-helper 1/T-helper 2 (Th1/Th2) aortic response toward an anti-inflammatory state (decreased aortic interleukin [IL] 2 to IL-10 and IL-2 to IL-13 expression ratios). Plaque smooth muscle cell content was similarly increased (128% and 141%, respectively). Aortic AT1 and AT2 receptor expression as well as aortic CD11c/CD206 and IL-1β/IL-1ra expression ratios were not significantly modulated by either RUN or TEL.
  
  
  CONCLUSIONS
  Running exercise and telmisartan treatment are equally effective in preventing Ang II-mediated plaque vulnerability but through distinct cellular and molecular mechanisms. Our findings further support the use of exercise training and selective AT1 receptor blocker therapies for atherosclerotic cardiovascular disease prevention.
authors.affiliation: 1 Division of Angiology, University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: Maxime
authors.initials: M
authors.lastname: Pellegrin
authors.affiliation: 1 Division of Angiology, University Hospital of Lausanne, Lausanne, Switzerland.|2 Sciences Séparatives Biologiques et Pharmaceutiques, UFR STAPS/SMP, Université de Franche-Comté, Besançon, France.
authors.forename: Justyna
authors.initials: J
authors.lastname: Szostak
authors.affiliation: 1 Division of Angiology, University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: Karima
authors.initials: K
authors.lastname: Bouzourène
authors.affiliation: 1 Division of Angiology, University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Aubert
authors.affiliation: 2 Sciences Séparatives Biologiques et Pharmaceutiques, UFR STAPS/SMP, Université de Franche-Comté, Besançon, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Berthelot
authors.affiliation: 1 Division of Angiology, University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: Jürg
authors.initials: J
authors.lastname: Nussberger
authors.affiliation: 3 Laboratoire Pharm-Ecologie Cardiovasculaire, UFRip Sciences Technologie et Santé, Université Avignon et des Pays de Vaucluse, Avignon, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Laurant
authors.affiliation: 1 Division of Angiology, University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: Lucia
authors.initials: L
authors.lastname: Mazzolai
keywords: PPARs; Th1/Th2 balance; angiotensin II; atherosclerosis; running exercise; telmisartan; vulnerable plaque