Overexpression of Peroxiredoxin 4 Attenuates Atherosclerosis in Apolipoprotein E Knockout Mice

Overview

Journal Antioxid Redox Signal

Specialty Endocrinology

Date 2012 May 3

PMID 22548251

Citations 32

Authors

Xin Guo

Sohsuke Yamada

Akihide Tanimoto

Yan Ding

Ke-Yong Wang

Shohei Shimajiri

Yoshitaka Murata

Satoshi Kimura

Takashi Tasaki

Atsunori Nabeshima

Teruo Watanabe

Kimitoshi Kohno

Yasuyuki Sasaguri

Affiliations

Soon will be listed here.

Abstract

Aim: A growing body of evidence has shown that increased formation of oxidized molecules and reactive oxygen species within the vasculature (i.e., the extracellular space) plays a crucial role in the initiation and progression of atherosclerosis and in the formation of unstable plaques. Peroxiredoxin 4 (PRDX4) is the only known secretory member of the antioxidant PRDX family. However, the relationship between PRDX4 and susceptibility to atherosclerosis has remained unclear.

Results: To define the role of PRDX4 in hyperlipidemia-induced atherosclerosis, we generated hPRDX4 transgenic (Tg) and apolipoprotein E (apoE) knockout mice (hPRDX4(+/+)/apoE(-/-)). After feeding the mice a high-cholesterol diet, they showed fewer atheromatous plaques, less T-lymphocyte infiltration, lower levels of oxidative stress markers, less necrosis, a larger number of smooth muscle cells, and a larger amount of collagen, resulting in thickened fibrous cap formation and possible stable plaque phenotype as compared with apoE(-/-) mice. We also detected greater suppression of apoptosis and decreased Bax expression in hPRDX4(+/+)/apoE(-/-) mice than in apoE(-/-) mice. Bone marrow transplantation from hPRDX4(+/+) donors to apoE(-/-) mice confirmed the antiatherogenic aspects of PRDX4, revealing significantly suppressed atherosclerotic progression.

Innovation: In this study, we demonstrated for the first time that PRDX4 suppressed the development of atherosclerosis in apoE(-/-) mice fed a high-cholesterol diet.

Conclusion: These data indicate that PRDX4 is an antiatherogenic factor and, by suppressing oxidative damage and apoptosis, that it may protect against the formation of vulnerable (unstable) plaques.

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