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Title

Swimming prevents vulnerable atherosclerotic plaque development in hypertensive 2-kidney, 1-clip mice by modulating angiotensin II type 1 receptor expression independently from hemodynamic changes

Authors
Pellegrin, Maxime
Alonso, Florian
Bouzourene, Karima
Haefliger, Jacques-Antoine
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Published in Hypertension. 2009, vol. 53, no. 5, p. 782-789
Abstract Exercise is known to reduce cardiovascular risk. However, its role on atherosclerotic plaque stabilization is unknown. Apolipoprotein E(-/-) mice with vulnerable (2-kidney, 1-clip: angiotensin [Ang] II-dependent hypertension model) or stable atherosclerotic plaques (1-kidney, 1-clip: Ang II-independent hypertension model and normotensive shams) were used for experiments. Mice swam regularly for 5 weeks and were compared with sedentary controls. Exercised 2-kidney, 1-clip mice developed significantly more stable plaques (thinner fibrous cap, decreased media degeneration, layering, macrophage content, and increased smooth muscle cells) than sedentary controls. Exercise did not affect blood pressure. Conversely, swimming significantly reduced aortic Ang II type 1 receptor mRNA levels, whereas Ang II type 2 receptor expression remained unaffected. Sympathetic tone also significantly diminished in exercised 2-kidney, 1-clip mice compared with sedentary ones; renin and aldosterone levels tended to increase. Ang II type 1 downregulation was not accompanied by improved endothelial function, and no difference in balance among T-helper 1, T-helper 2, and T regulatory cells was observed between sedentary and exercised mice. These results show for the first time, in a mouse model of Ang II-mediated vulnerable plaques, that swimming prevents atherosclerosis progression and plaque vulnerability. This benefit is likely mediated by downregulating aortic Ang II type 1 receptor expression independent from any hemodynamic change. Ang II type 1 downregulation may protect the vessel wall from the Ang II proatherogenic effects. Moreover, data presented herein further emphasize the pivotal and blood pressure-independent role of Ang II in atherogenesis.
Keywords Aldosterone/bloodAnimalsApolipoproteins E/physiologyAtherosclerosis/*prevention & control*Blood PressureCholesterol/bloodCitrate (si)-Synthase/blood*Heart RateHypertension/*complications/physiopathologyInterleukin-6/bloodMiceMice, Inbred C57BLNitric Oxide Synthase Type III/geneticsNorepinephrine/bloodRNA, Messenger/analysisReceptor, Angiotensin, Type 1/*geneticsRenin/blood*Swimming
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PMID: 19349555
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Structures
Research groups Biologie du myocarde (22)
L'athérosclérose et ses complications cliniques (591)
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PELLEGRIN, Maxime et al. Swimming prevents vulnerable atherosclerotic plaque development in hypertensive 2-kidney, 1-clip mice by modulating angiotensin II type 1 receptor expression independently from hemodynamic changes. In: Hypertension, 2009, vol. 53, n° 5, p. 782-789. https://archive-ouverte.unige.ch/unige:20025

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Deposited on : 2012-04-23

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