Peroxiredoxin1 Prevents Excessive Endothelial Activation and Early Atherosclerosis

Janka KISUCKA; Anil K CHAUHAN; Ian S PATTEN; Ayce YESILALTAY; Carola NEUMANN; Richard A VAN ETTEN; Monty KRIEGER; Denisa D WAGNER

doi:10.1161/CIRCRESAHA.108.174870

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Peroxiredoxin1 Prevents Excessive Endothelial Activation and Early Atherosclerosis

Journal article

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Peroxiredoxin1 Prevents Excessive Endothelial Activation and Early Atherosclerosis

Janka KISUCKA, Anil K CHAUHAN, Ian S PATTEN, Ayce YESILALTAY, Carola NEUMANN, Richard A VAN ETTEN, Monty KRIEGER and Denisa D WAGNER

Circulation research, Vol.103(6), pp.598-605

2008

DOI: 10.1161/CIRCRESAHA.108.174870

PMCID: PMC4911701

PMID: 18689572

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Abstract

The peroxiredoxin (Prdx) family of antioxidant enzymes uses redox-active cysteines to reduce peroxides, lipid hydroperoxides, and peroxynitrites. Prdx1 is known to be important to protect red blood cells against reactive oxygen species and in tumor prevention. In this study, the role of Prdx1 in inflammation, thrombosis, and atherosclerosis was investigated. Using intravital microscopy, we showed that the number of leukocytes rolling per minute in unstimulated veins was increased by 2.5-fold in Prdx1(-/-) compared to Prdx1(+/+) mice. In Prdx1(-/-) mice, 50% of leukocytes rolled at a velocity <10 mum/sec compared with 10% in Prdx1(+/+) mice, suggesting that adhesion molecule density on the endothelium may have been increased by Prdx1 deficiency. Indeed, endothelial P-selectin, soluble P-selectin, and von Willebrand factor in plasma were increased in Prdx1(-/-) mice compared to Prdx1(+/+) mice, indicating elevated Weibel-Palade body release. In contrast to this excessive endothelial activation, Prdx1(-/-) platelets showed no sign of hyperreactivity, and their aggregation both in vitro and in vivo was normal. We also examined the role of Prdx1 in the apoE(-/-) murine spontaneous model of atherosclerosis. Prdx1(-/-)/apoE(-/-) mice fed normal chow developed larger, more macrophage-rich aortic sinus lesions than Prdx1(+/+)/apoE(-/-) mice, despite similar amounts and size distributions of cholesterol in their plasma lipoproteins. Thus, Prdx1 protects against excessive endothelial activation and atherosclerosis, and the Prdx1(-/-) mice could serve as an animal model susceptible to chronic inflammation.

Fundamental and applied biological sciences. Psychology

Cardiology. Vascular system

Atherosclerosis (general aspects, experimental research)

Biological and medical sciences

Medical sciences

Vertebrates: cardiovascular system

Blood and lymphatic vessels

Details

Title: Subtitle: Peroxiredoxin1 Prevents Excessive Endothelial Activation and Early Atherosclerosis
Creators: Janka KISUCKA - Immune Disease Institute Inc, Harvard Medical School, Boston, Mass, United States
Anil K CHAUHAN - Immune Disease Institute Inc, Harvard Medical School, Boston, Mass, United States
Ian S PATTEN - Immune Disease Institute Inc, Harvard Medical School, Boston, Mass, United States
Ayce YESILALTAY - Department of Biology Massachusetts Institute of Technology, Cambridge, Mass, United States
Carola NEUMANN - Medical University of South Carolina Cell and Molecular Pharmacology, Charleston, United States
Richard A VAN ETTEN - Molecular Oncology Research Institute Tufts-New England Medical Center, Boston, Mass, United States
Monty KRIEGER - Department of Biology Massachusetts Institute of Technology, Cambridge, Mass, United States
Denisa D WAGNER - Immune Disease Institute Inc, Harvard Medical School, Boston, Mass, United States
Resource Type: Journal article
Publication Details: Circulation research, Vol.103(6), pp.598-605
DOI: 10.1161/CIRCRESAHA.108.174870
PMID: 18689572
PMCID: PMC4911701
NLM abbreviation: Circ Res
ISSN: 0009-7330
eISSN: 1524-4571
Publisher: Lippincott
Language: English
Date published: 2008
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984094554302771

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