title: Effects of N-acetyl-seryl-asparyl-lysyl-proline on blood pressure, renal damage, and mortality in systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease with a high prevalence of hypertension. NZBWF1 (SLE-Hyp) mice develop hypertension that can be prevented by modulating T cells. The peptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) decreases renal damage and improves renal function in a model of SLE without hypertension (MRL/lpr). However, it is not known whether Ac-SDKP prevents hypertension in NZBWF1 mice. We hypothesized that in SLE-Hyp, Ac-SDKP prevents hypertension and renal damage by modulating T cells. Animals were divided into four groups: (1) control + vehicle, (2) control + Ac-SDKP, (3) SLE + vehicle, and (4) SLE + Ac-SDKP Systolic blood pressure (SBP), albuminuria, renal fibrosis, and T-cell phenotype were analyzed. SBP was higher in SLE compared to control mice and was not decreased by Ac-SDKP treatment. Half of SLE mice developed an acute and severe form of hypertension accompanied by albuminuria followed by death. Ac-SDKP delayed development of severe hypertension, albuminuria, and early mortality, but this delay did not reach statistical significance. Ac-SDKP prevented glomerulosclerosis, but not interstitial fibrosis in SLE-Hyp mice. SLE-Hyp mice showed a decrease in helper and cytotoxic T cells as well as an increase in double negative lymphocytes and T helper 17 cells, but these cells were unaffected by Ac-SDKP In conclusion, Ac-SDKP prevents kidney damage, without affecting blood pressure in an SLE animal model. However, during the acute relapse of SLE, Ac-SDKP might also delay the manifestation of an acute and severe form of hypertension leading to early mortality. Ac-SDKP is a potential tool to treat renal damage in SLE-Hyp mice.
authors.affiliation: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Pablo
authors.initials: P
authors.lastname: Nakagawa
authors.affiliation: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Juan X
authors.initials: JX
authors.lastname: Masjoan-Juncos
authors.affiliation: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Heba
authors.initials: H
authors.lastname: Basha
authors.affiliation: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Branislava
authors.initials: B
authors.lastname: Janic
authors.affiliation: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Morel E
authors.initials: ME
authors.lastname: Worou
authors.affiliation: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Tang-Dong
authors.initials: TD
authors.lastname: Liao
authors.affiliation: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Cesar A
authors.initials: CA
authors.lastname: Romero
authors.affiliation: Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Peterson
authors.affiliation: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan ocarret1@hfhs.org.
authors.forename: Oscar A
authors.initials: OA
authors.lastname: Carretero
mesh_terms: D000419:Albuminuria / Q000517:prevention & control; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005355:Fibrosis / Q000517:prevention & control; D006973:Hypertension / Q000150:complications / Q000276:immunology* / Q000517:prevention & control; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000401:mortality / Q000503:physiopathology*; D051379:Mice; D009842:Oligopeptides / Q000008:administration & dosage* / Q000627:therapeutic use; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D009842:Oligopeptides; C058504:goralatide
keywords: Ac‐SDKP; NZBWF1; hypertension; lupus