Arginase I enhances atherosclerotic plaque stabilization by inhibiting inflammation and promoting smooth muscle cell proliferation - PubMed (original) (raw)

Arginase I enhances atherosclerotic plaque stabilization by inhibiting inflammation and promoting smooth muscle cell proliferation

Xu-Ping Wang et al. Eur Heart J. 2014 Apr.

Abstract

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.

Keywords: Arginase I; Atherosclerotic plaque stability; Inflammation; Proliferation.

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