title: Immunization with an ApoB-100 Related Peptide Vaccine Attenuates Angiotensin-II Induced Hypertension and Renal Fibrosis in Mice.
abstract: Recent studies suggest the potential involvement of CD8+ T cells in the pathogenesis of murine hypertension. We recently reported that immunization with apoB-100 related peptide, p210, modified CD8+ T cell function in angiotensin II (AngII)-infused apoE (-/-) mice. In this study, we hypothesized that p210 vaccine modulates blood pressure in AngII-infused apoE (-/-) mice. Male apoE (-/-) mice were immunized with p210 vaccine and compared to unimmunized controls. At 10 weeks of age, mice were subcutaneously implanted with an osmotic pump which released AngII for 4 weeks. At 13 weeks of age, p210 immunized mice showed significantly lower blood pressure response to AngII compared to controls. CD8+ T cells from p210 immunized mice displayed a different phenotype compared to CD8+ T cells from unimmunized controls. Serum creatinine and urine albumin to creatinine ratio were significantly decreased in p210 immunized mice suggesting that p210 vaccine had renal protective effect. At euthanasia, inflammatory genes IL-6, TNF-α, and MCP-1 in renal tissue were down-regulated by p210 vaccine. Renal fibrosis and pro-fibrotic gene expression were also significantly reduced in p210 immunized mice. To assess the role of CD8+ T cells in these beneficial effects of p210 vaccine, CD8+ T cells were depleted by CD8 depleting antibody in p210 immunized mice. p210 immunized mice with CD8+ T cell depletion developed higher blood pressure compared to mice receiving isotype control. Depletion of CD8+ T cells also increased renal fibrotic gene expression compared to controls. We conclude that immunization with p210 vaccine attenuated AngII-induced hypertension and renal fibrosis. CD8+ T cells modulated by p210 vaccine could play an important role in the anti-hypertensive, anti-fibrotic and renal-protective effect of p210 vaccine.
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Honjo
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Kuang-Yuh
authors.initials: KY
authors.lastname: Chyu
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Dimayuga
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Wai Man
authors.initials: WM
authors.lastname: Lio
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Juliana
authors.initials: J
authors.lastname: Yano
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Portia
authors.initials: P
authors.lastname: Trinidad
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Jianchang
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Bojan
authors.initials: B
authors.lastname: Cercek
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Prediman K
authors.initials: PK
authors.lastname: Shah
mesh_terms: D000804:Angiotensin II / Q000009:adverse effects*; D000818:Animals; D053299:Apolipoprotein B-100 / Q000737:chemistry / Q000276:immunology*; D001794:Blood Pressure; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D015870:Gene Expression; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D007114:Immunization; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D000074624:NADPH Oxidase 1; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D017382:Reactive Oxygen Species; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D022223:Vaccines, Subunit
chemical_list: D053299:Apolipoprotein B-100; D016207:Cytokines; D010455:Peptides; D017382:Reactive Oxygen Species; D022223:Vaccines, Subunit; D000804:Angiotensin II; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1