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Publication : Transplantation of periaortic adipose tissue inhibits atherosclerosis in apoE<sup>-/-</sup> mice by evoking TGF-β1-mediated anti-inflammatory response in transplanted graft.

First Author  Terada K Year  2018
Journal  Biochem Biophys Res Commun Volume  501
Issue  1 Pages  145-151
PubMed ID  29705699 Mgi Jnum  J:270307
Mgi Id  MGI:6276682 Doi  10.1016/j.bbrc.2018.04.196
Citation  Terada K, et al. (2018) Transplantation of periaortic adipose tissue inhibits atherosclerosis in apoE(-/-) mice by evoking TGF-beta1-mediated anti-inflammatory response in transplanted graft. Biochem Biophys Res Commun 501(1):145-151
abstractText  Perivascular adipose tissue (PAT) is associated with vascular homeostasis; however, its causal effect on atherosclerosis currently remains undefined. Here, we investigated the effect of experimental PAT transplantation on atherosclerosis. The thoracic periaortic adipose tissue (tPAT) was dissected from 16-week-old wild-type mice and transplanted over the infrarenal aorta of 20-week-old apoE deficient (apoE(-/-)) mice fed high-cholesterol diet for 3 months. Oil-red O staining after 4 weeks showed a significant 20% decrease in the atherosclerotic lesion of suprarenal aorta compared with that of sham control mice, while that of infrarenal aorta showed no difference between the two groups. TGF-beta1 mRNA expression was significantly higher in grafted tPAT than donor tPAT, accompanied by a significant increase in serum TGF-beta1 concentration, which was inversely correlated with the suprarenal lesion area (r=-0.63, P=0.012). Treatment with neutralizing TGF-beta antibody abrogated the anti-atherogenic effect of tPAT transplantation. Immunofluorescent analysis of grafted tPAT showed that TGF-beta-positive cells were co-localized with Mac-2-positive cells and this number was significantly increased compared with donor tPAT. There was also marked increase in mRNA expression of alternatively activated macrophages-related genes. Furthermore, the percentage of eosinophils in stromal vascular fraction of donor tPAT was much higher than that in epididymal white adipose tissue, concomitant with the significantly higher protein level of IL-4. IL-4 mRNA expression levels in grafted tPAT were increased in a time-dependent manner after tPAT transplantation. Our findings show that tPAT transplantation inhibits atherosclerosis development by exerting TGF-beta1-mediated anti-inflammatory response, which may involve alternatively activated macrophages.
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