Protective role of uncoupling protein 2 in atherosclerosis.

Abstract:

BACKGROUND:Uncoupling protein 2 (UCP2) regulates the production of reactive oxygen species in macrophages. However, its role in atherosclerosis is unknown. METHODS AND RESULTS:Irradiated low-density lipoprotein receptor deficient mice (LDLR-/-) were transplanted with bone marrow from either UCP2 deficient mice (Ucp2-/-) or wild type mice (Ucp2+/+). Mice were fed an atherogenic diet for 7 weeks. Engraftment of bone marrow cells was confirmed by the presence of UCP2 protein expression in spleen cell mitochondria of Ucp2+/+ transplanted mice and its absence in Ucp2-/- transplanted mice. Leukocyte counts and plasma cholesterol levels were comparable in both groups. We found a marked increase in atherosclerotic lesion size in the thoracic aorta of Ucp2-/- transplanted mice compared with control Ucp2+/+ transplanted mice (8.3+/-0.9% versus 4.3+/-0.4%, respectively; P<0.005), as well as in the aortic sinus (150 066+/-12 388 microm2 versus 105 689+/-9 727 microm2, respectively; P<0.05). This was associated with increased nitrotyrosine staining, which suggests enhanced oxidative stress. Analysis of plaque composition revealed a significant increase in macrophage accumulation (P<0.05) and apoptosis (P<0.05), along with a decrease in collagen content (P<0.05), suggesting a potentially more vulnerable phenotype. CONCLUSION:These results suggest a protective role for UCP2 against atherosclerosis.

journal_name

Circulation

journal_title

Circulation

authors

Blanc J,Alves-Guerra MC,Esposito B,Rousset S,Gourdy P,Ricquier D,Tedgui A,Miroux B,Mallat Z

doi

10.1161/01.cir.0000051722.66074.60

subject

Has Abstract

pub_date

2003-01-28 00:00:00

pages

388-90

issue

3

eissn

0009-7322

issn

1524-4539

journal_volume

107

pub_type

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