Vascular respiratory uncoupling increases blood pressure and atherosclerosis.

Abstract:

:The observations that atherosclerosis often occurs in non-smokers without elevated levels of low-density lipoprotein cholesterol, and that most atherosclerosis loci so far identified in mice do not affect systemic risk factors associated with atherosclerosis, suggest that as-yet-unidentified mechanisms must contribute to vascular disease. Arterial walls undergo regional disturbances of metabolism that include the uncoupling of respiration and oxidative phosphorylation, a process that occurs to some extent in all cells and may be characteristic of blood vessels being predisposed to the development of atherosclerosis. To test the hypothesis that inefficient metabolism in blood vessels promotes vascular disease, we generated mice with doxycycline-inducible expression of uncoupling protein-1 (UCP1) in the artery wall. Here we show that UCP1 expression in aortic smooth muscle cells causes hypertension and increases dietary atherosclerosis without affecting cholesterol levels. UCP1 expression also increases superoxide production and decreases the availability of nitric oxide, evidence of oxidative stress. These results provide proof of principle that inefficient metabolism in blood vessels can cause vascular disease.

journal_name

Nature

journal_title

Nature

authors

Bernal-Mizrachi C,Gates AC,Weng S,Imamura T,Knutsen RH,DeSantis P,Coleman T,Townsend RR,Muglia LJ,Semenkovich CF

doi

10.1038/nature03527

keywords:

subject

Has Abstract

pub_date

2005-05-26 00:00:00

pages

502-6

issue

7041

eissn

0028-0836

issn

1476-4687

pii

nature03527

journal_volume

435

pub_type

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