Rictor in Perivascular Adipose Tissue Controls Vascular Function by Regulating Inflammatory Molecule Expression

Bhattacharya, I. and Drägert, K. and Albert, V. and Contassot, E. and Damjanovic, M. and Hagiwara, A. and Zimmerli, L. and Humar, R. and Hall, M. N. and Battegay, E. J. and Haas, E.. (2013) Rictor in Perivascular Adipose Tissue Controls Vascular Function by Regulating Inflammatory Molecule Expression. Arteriosclerosis, thrombosis, and vascular biology, Vol. 33, H. 9. pp. 2105-2111.

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Official URL: http://edoc.unibas.ch/dok/A6165090

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Perivascular adipose tissue (PVAT) wraps blood vessels and modulates vasoreactivity by secretion of vasoactive molecules. Mammalian target of rapamycin complex 2 (mTORC2) has been shown to control inflammation and is expressed in adipose tissue. In this study, we investigated whether adipose-specific deletion of rictor and thereby inactivation of mTORC2 in PVAT may modulate vascular function by increasing inflammation in PVAT.; Rictor, an essential mTORC2 component, was deleted specifically in mouse adipose tissue (rictor(ad-/-)). Phosphorylation of mTORC2 downstream target Akt at Serine 473 was reduced in PVAT from rictor(ad-/-) mice but unaffected in aortic tissue. Ex vivo functional analysis of thoracic aortae revealed increased contractions and impaired dilation in rings with PVAT from rictor(ad-/-) mice. Adipose rictor knockout increased gene expression and protein release of interleukin-6, macrophage inflammatory protein-1α, and tumor necrosis factor-α in PVAT as shown by quantitative real-time polymerase chain reaction and Bioplex analysis for the cytokines in the conditioned media, respectively. Moreover, gene and protein expression of inducible nitric oxide synthase was upregulated without affecting macrophage infiltration in PVAT from rictor(ad-/-) mice. Inhibition of inducible nitric oxide synthase normalized vascular reactivity in aortic rings from rictor(ad-/-) mice with no effect in rictor(fl/fl) mice. Interestingly, in perivascular and epididymal adipose depots, high-fat diet feeding induced downregulation of rictor gene expression.; Here, we identify mTORC2 as a critical regulator of PVAT-directed protection of normal vascular tone. Modulation of mTORC2 activity in adipose tissue may be a potential therapeutic approach for inflammation-related vascular damage.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
UniBasel Contributors:Hall, Michael N.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Heart Association
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:13 Sep 2013 07:59
Deposited On:13 Sep 2013 07:52

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