From: Rafal Smigrodzki (rms2g@virginia.edu)
Date: Thu Jan 30 2003 - 15:02:04 MST
I found an interesting article today:
Protective role of uncoupling protein 2 in atherosclerosis.
Blanc J, Alves-Guerra MC, Esposito B, Rousset S, Gourdy P, Ricquier D,
Tedgui A, Miroux B, Mallat Z.
Institut National de la Sante et de la Recherche Medicale, INSERM U541, and
Institut Federatif de Recherche, IFR Circulation, Universite Paris VII,
Hopital Lariboisiere, Paris, France (J.B., B.E., A.T., Z.M.).
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 micro m(2) versus 105 689+/-9
727 micro m(2), 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.
### If indeed there is a protective role of uncouplers (UCP1, 2 and 3)
against the production of ROS, this would offer a way of dealing with the
chronical energy overload our mitos are laboring under (except in persons on
CR). If we could induce uncouplers pharmacologically, we could reduce the
mitochondrial membrane potential just enough to cut ROS production, but not
enough to cause ATP deficiency. As a side effect we could eat a lot, never
get obese, and feel warm all the time.
Rafal
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