Protective role of uncoupling protein 2 in atherosclerosis.
BACKGROUND
Uncoupling protein 2 (UCP2) regulates the production of reactive oxygen species in macrophages. However, its role in atherosclerosis is unknown.


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.


CONCLUSIONS
These results suggest a protective role for UCP2 against atherosclerosis.
Blanc
J
J
Institut National de la Santé et de la Recherche Médicale, INSERM U541, and Université Paris VII, Hôpital Lariboisière, Paris, France.
Alves-Guerra
M C
MC
Esposito
B
B
Rousset
S
S
Gourdy
P
P
Ricquier
D
D
Tedgui
A
A
Miroux
B
B
Mallat
Z
Z
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology* / Q000473:pathology; D016026:Bone Marrow Transplantation; D002316:Cardiotonic Agents; D002784:Cholesterol / Q000097:blood; D005260:Female; D007473:Ion Channels; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins; D018384:Oxidative Stress; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D011973:Receptors, LDL / Q000235:genetics; D000071246:Uncoupling Protein 2
D002316:Cardiotonic Agents; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D011973:Receptors, LDL; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D002784:Cholesterol