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

Nathan C. Sundgren, Wanpen Vongpatanasin, Brigid Meghan D Boggan, Keiji Tanigaki, Ivan S. Yuhanna, Ken L. Chambliss, Chieko Mineo, Philip W. Shaul

Research output: Contribution to journalArticle

11 Scopus citations

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 Fcγ receptor IIB (FcγRIIB) 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 FcγRIIB 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 FcγRIIB 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 FcγRIIB mice developed obesity-induced hypertension, FcγRIIB 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; FcγRIIB 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 FcγRIIB-dependent process. Thus, we have identified a novel role for FcγRIIB 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 FcγRIIB may potentially offer new means to treat hypertension in obese individuals.

Original languageEnglish (US)
Pages (from-to)456-462
Number of pages7
JournalHypertension
Volume65
Issue number2
DOIs
StatePublished - Feb 21 2015

Keywords

  • C-reactive protein
  • IgG
  • hypertension
  • inflammation
  • obesity
  • serum amyloid P component

ASJC Scopus subject areas

  • Internal Medicine

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