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

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.

journal_name

Eur Heart J

journal_title

European heart journal

authors

Wang XP,Zhang W,Liu XQ,Wang WK,Yan F,Dong WQ,Zhang Y,Zhang MX

doi

10.1093/eurheartj/eht329

subject

Has Abstract

pub_date

2014-04-01 00:00:00

pages

911-9

issue

14

eissn

0195-668X

issn

1522-9645

pii

eht329

journal_volume

35

pub_type

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