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 μm 2 versus 105 689±9 727 μm 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.