Running Exercise and Angiotensin II Type I Receptor Blocker Telmisartan Are Equally Effective in Preventing Angiotensin II-Mediated Vulnerable Atherosclerotic Lesions. (March 2017)

• Record Type: Journal Article
• Authors: Pellegrin, Maxime; Szostak, Justyna; Bouzourène, Karima; Aubert, Jean-François; Berthelot, Alain; Nussberger, Jürg; Laurant, Pascal; Mazzolai, Lucia
• Is Part Of: Journal of cardiovascular pharmacology and therapeutics. Volume 22:Number 2(2017:Mar.)
• Page Start: 159
• Page End: 168
• Publication Date: 2017-03
• Subjects: atherosclerosis -- vulnerable plaque -- angiotensin II -- running exercise -- telmisartan -- PPARs -- Th1/Th2 balance; Cardiovascular pharmacology -- Periodicals; Cardiovascular system -- Diseases -- Treatment -- Periodicals; 616
• DOI: 10.1177/1074248416652235
• Languages: English
• ISSNs: 1074-2484

Abstract

Introduction: 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. Materials and 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. Conclusion: 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.