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IgG receptor Fc?RIIB plays a key role in obesity-induced hypertension.

ABSTRACT: There is a well-recognized association between obesity, inflammation, and hypertension. Why obesity causes hypertension is poorly understood. We previously demonstrated using a C-reactive protein (CRP) transgenic mouse that CRP induces hypertension that is related to NO deficiency. Our prior work in cultured endothelial cells identified the Fc? receptor IIB (Fc?RIIB) as the receptor for CRP whereby it antagonizes endothelial NO synthase. Recognizing known associations between CRP and obesity and hypertension in humans, in the present study we tested the hypothesis that Fc?RIIB plays a role in obesity-induced hypertension in mice. Using radiotelemetry, we first demonstrated that the hypertension observed in transgenic mouse-CRP is mediated by the receptor, indicating that Fc?RIIB is capable of modifying blood pressure. We then discovered in a model of diet-induced obesity yielding equal adiposity in all study groups that whereas Fc?RIIB(+/+) mice developed obesity-induced hypertension, Fc?RIIB(-/-) mice were fully protected. Levels of CRP, the related pentraxin serum amyloid P component which is the CRP-equivalent in mice, and total IgG were unaltered by diet-induced obesity; Fc?RIIB expression in endothelium was also unchanged. However, whereas IgG isolated from chow-fed mice had no effect, IgG from high-fat diet-fed mice inhibited endothelial NO synthase in cultured endothelial cells, and this was an Fc?RIIB-dependent process. Thus, we have identified a novel role for Fc?RIIB in the pathogenesis of obesity-induced hypertension, independent of processes regulating adiposity, and it may entail an IgG-induced attenuation of endothelial NO synthase function. Approaches targeting Fc?RIIB may potentially offer new means to treat hypertension in obese individuals.

SUBMITTER: Sundgren NC

PROVIDER: S-EPMC4419357 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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IgG receptor FcγRIIB plays a key role in obesity-induced hypertension.

Sundgren Nathan C NC Vongpatanasin Wanpen W Boggan Brigid-Meghan D BM Tanigaki Keiji K Yuhanna Ivan S IS Chambliss Ken L KL Mineo Chieko C Shaul Philip W PW

Hypertension (Dallas, Tex. : 1979) 20141103 2

There is a well-recognized association between obesity, inflammation, and hypertension. Why obesity causes hypertension is poorly understood. We previously demonstrated using a C-reactive protein (CRP) transgenic mouse that CRP induces hypertension that is related to NO deficiency. Our prior work in cultured endothelial cells identified the Fcγ receptor IIB (FcγRIIB) as the receptor for CRP whereby it antagonizes endothelial NO synthase. Recognizing known associations between CRP and obesity and ...[more]

PMID: 25368023

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IgG receptor Fc?RIIB plays a key role in obesity-induced hypertension.

Publications

IgG receptor FcγRIIB plays a key role in obesity-induced hypertension.

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