| First Author | Sundgren NC | Year | 2015 |
| Journal | Hypertension | Volume | 65 |
| Issue | 2 | Pages | 456-62 |
| PubMed ID | 25368023 | Mgi Jnum | J:283131 |
| Mgi Id | MGI:6368257 | Doi | 10.1161/HYPERTENSIONAHA.114.04670 |
| Citation | Sundgren NC, et al. (2015) IgG receptor FcgammaRIIB plays a key role in obesity-induced hypertension. Hypertension 65(2):456-62 |
| abstractText | 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 Fcgamma receptor IIB (FcgammaRIIB) 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 FcgammaRIIB 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 FcgammaRIIB 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 FcgammaRIIB(+/+) mice developed obesity-induced hypertension, FcgammaRIIB(-/-) 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; FcgammaRIIB 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 FcgammaRIIB-dependent process. Thus, we have identified a novel role for FcgammaRIIB 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 FcgammaRIIB may potentially offer new means to treat hypertension in obese individuals. |
