AIMS: The aim of this study was to investigate the effect of Arginase I (ArgI) on plaque stabilization in unruptured atherosclerotic plaque and explore its mechanism. METHODS AND RESULTS: The atherosclerotic plaque model was established in New Zealand rabbits by balloon injury of abdominal arteries and a high cholesterol (1%) diet. Arginase I overexpression reduced the content of macrophages and lipids and increased that of smooth muscle cells and collagen in the atherosclerotic plaque, thus contributing to decreased plaque vulnerability. Arginase I overexpression decreased the expression of the inflammatory cytokines tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) as well as inducible nitric oxide synthase (iNOS) in plaques. In vitro, ArgI overexpression or iNOS inhibition abolished the secretion of TNF-α and IL-6 induced by lipopolysaccharide in Raw264.7 cells. However, exogenous l-arginine restored the expression of inflammatory cytokines. Arginase I overexpression inhibited the activity of iNOS without changing its expression. Moreover, ArgI co-localized with iNOS in both Raw264.7 cells and human aortic atherosclerotic plaques. In addition, the IL-10 level was increased in plaque with ArgI overexpression. Finally, ArgI promoted aortic vascular smooth muscle cell proliferation, which was associated with increased production of intracellular polyamines. CONCLUSION: ArgI enhances the stability of atherosclerotic plaque by inhibiting the expression of inflammatory cytokines and stimulating smooth muscle cell proliferation.
AIMS: The aim of this study was to investigate the effect of Arginase I (ArgI) on plaque stabilization in unruptured atherosclerotic plaque and explore its mechanism. METHODS AND RESULTS: The atherosclerotic plaque model was established in New Zealand rabbits by balloon injury of abdominal arteries and a high cholesterol (1%) diet. Arginase I overexpression reduced the content of macrophages and lipids and increased that of smooth muscle cells and collagen in the atherosclerotic plaque, thus contributing to decreased plaque vulnerability. Arginase I overexpression decreased the expression of the inflammatory cytokines tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) as well as inducible nitric oxide synthase (iNOS) in plaques. In vitro, ArgI overexpression or iNOS inhibition abolished the secretion of TNF-α and IL-6 induced by lipopolysaccharide in Raw264.7 cells. However, exogenous l-arginine restored the expression of inflammatory cytokines. Arginase I overexpression inhibited the activity of iNOS without changing its expression. Moreover, ArgI co-localized with iNOS in both Raw264.7 cells and humanaortic atherosclerotic plaques. In addition, the IL-10 level was increased in plaque with ArgI overexpression. Finally, ArgI promoted aortic vascular smooth muscle cell proliferation, which was associated with increased production of intracellular polyamines. CONCLUSION:ArgI enhances the stability of atherosclerotic plaque by inhibiting the expression of inflammatory cytokines and stimulating smooth muscle cell proliferation.
Authors: Liyang Zhao; Alyssa J Cozzo; Amy R Johnson; Taylor Christensen; Alex J Freemerman; James E Bear; Jeremy D Rotty; Brian J Bennett; Liza Makowski Journal: Atherosclerosis Date: 2017-10-07 Impact factor: 5.162
Authors: Ángela Vinué; Jorge Navarro; Andrea Herrero-Cervera; Marta García-Cubas; Irene Andrés-Blasco; Sergio Martínez-Hervás; José T Real; Juan F Ascaso; Herminia González-Navarro Journal: Diabetologia Date: 2017-06-12 Impact factor: 10.122
Authors: Rogier A van Dijk; Kevin Rijs; Anouk Wezel; Jaap F Hamming; Frank D Kolodgie; Renu Virmani; Alexander F Schaapherder; Jan H N Lindeman Journal: J Am Heart Assoc Date: 2016-06-16 Impact factor: 5.501