title: IgG receptor FcγRIIB 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 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.
authors.affiliation: From the Department of Pediatrics, Section of Neonatology, Baylor College of Medicine, Houston, TX (N.C.S., B.-M.D.B.); and Department of Internal Medicine, Division of Cardiology, Hypertension Section (W.V.) and Department of Pediatrics, Center for Pulmonary and Vascular Biology (K.T., I.S.Y., K.L.C., C.M., P.W.S.), University of Texas Southwestern Medical Center, Dallas. sundgren@bcm.edu.
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Sundgren
authors.affiliation: From the Department of Pediatrics, Section of Neonatology, Baylor College of Medicine, Houston, TX (N.C.S., B.-M.D.B.); and Department of Internal Medicine, Division of Cardiology, Hypertension Section (W.V.) and Department of Pediatrics, Center for Pulmonary and Vascular Biology (K.T., I.S.Y., K.L.C., C.M., P.W.S.), University of Texas Southwestern Medical Center, Dallas.
authors.forename: Wanpen
authors.initials: W
authors.lastname: Vongpatanasin
authors.affiliation: From the Department of Pediatrics, Section of Neonatology, Baylor College of Medicine, Houston, TX (N.C.S., B.-M.D.B.); and Department of Internal Medicine, Division of Cardiology, Hypertension Section (W.V.) and Department of Pediatrics, Center for Pulmonary and Vascular Biology (K.T., I.S.Y., K.L.C., C.M., P.W.S.), University of Texas Southwestern Medical Center, Dallas.
authors.forename: Brigid-Meghan D
authors.initials: BM
authors.lastname: Boggan
authors.affiliation: From the Department of Pediatrics, Section of Neonatology, Baylor College of Medicine, Houston, TX (N.C.S., B.-M.D.B.); and Department of Internal Medicine, Division of Cardiology, Hypertension Section (W.V.) and Department of Pediatrics, Center for Pulmonary and Vascular Biology (K.T., I.S.Y., K.L.C., C.M., P.W.S.), University of Texas Southwestern Medical Center, Dallas.
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanigaki
authors.affiliation: From the Department of Pediatrics, Section of Neonatology, Baylor College of Medicine, Houston, TX (N.C.S., B.-M.D.B.); and Department of Internal Medicine, Division of Cardiology, Hypertension Section (W.V.) and Department of Pediatrics, Center for Pulmonary and Vascular Biology (K.T., I.S.Y., K.L.C., C.M., P.W.S.), University of Texas Southwestern Medical Center, Dallas.
authors.forename: Ivan S
authors.initials: IS
authors.lastname: Yuhanna
authors.affiliation: From the Department of Pediatrics, Section of Neonatology, Baylor College of Medicine, Houston, TX (N.C.S., B.-M.D.B.); and Department of Internal Medicine, Division of Cardiology, Hypertension Section (W.V.) and Department of Pediatrics, Center for Pulmonary and Vascular Biology (K.T., I.S.Y., K.L.C., C.M., P.W.S.), University of Texas Southwestern Medical Center, Dallas.
authors.forename: Ken L
authors.initials: KL
authors.lastname: Chambliss
authors.affiliation: From the Department of Pediatrics, Section of Neonatology, Baylor College of Medicine, Houston, TX (N.C.S., B.-M.D.B.); and Department of Internal Medicine, Division of Cardiology, Hypertension Section (W.V.) and Department of Pediatrics, Center for Pulmonary and Vascular Biology (K.T., I.S.Y., K.L.C., C.M., P.W.S.), University of Texas Southwestern Medical Center, Dallas.
authors.forename: Chieko
authors.initials: C
authors.lastname: Mineo
authors.affiliation: From the Department of Pediatrics, Section of Neonatology, Baylor College of Medicine, Houston, TX (N.C.S., B.-M.D.B.); and Department of Internal Medicine, Division of Cardiology, Hypertension Section (W.V.) and Department of Pediatrics, Center for Pulmonary and Vascular Biology (K.T., I.S.Y., K.L.C., C.M., P.W.S.), University of Texas Southwestern Medical Center, Dallas.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Shaul
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002097:C-Reactive Protein / Q000009:adverse effects / Q000032:analysis / Q000235:genetics; D002478:Cells, Cultured; D004041:Dietary Fats / Q000633:toxicity; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D006973:Hypertension / Q000209:etiology* / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology; D007249:Inflammation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000502:physiology*; D009765:Obesity / Q000150:complications* / Q000276:immunology; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000683:Serum Amyloid P-Component / Q000032:analysis
chemical_list: D004041:Dietary Fats; C499172:Fcgr2b protein, mouse; D007074:Immunoglobulin G; D017452:Receptors, IgG; D000683:Serum Amyloid P-Component; D009569:Nitric Oxide; D002097:C-Reactive Protein; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse
keywords: C-reactive protein; IgG; hypertension; inflammation; obesity; serum amyloid P component