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: Pablo Nakagawa, Juan X Masjoan-Juncos, Heba Basha, Branislava Janic, Morel E Worou, Tang-Dong Liao, Cesar A Romero, Edward L Peterson, Oscar A Carretero
• Journal: Physiological reports (Physiol Rep) Vol. 5 Issue 2 (Jan 2017) ISSN: 2051-817X [Electronic] United States
• PMID: 28126732 (Publication Type: Journal Article)
• Copyright: © 2017 Henry Ford Health System. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Chemical References

• Oligopeptides
• goralatide

Topics

• Albuminuria (prevention & control)
• Animals
• Blood Pressure (drug effects)
• Female
• Fibrosis (prevention & control)
• Hypertension (complications, immunology, prevention & control)
• Kidney (drug effects, pathology)
• Kidney Diseases (complications, immunology, pathology, prevention & control)
• Lupus Erythematosus, Systemic (complications, mortality, physiopathology)
• Mice
• Oligopeptides (administration & dosage, therapeutic use)
• Survival Analysis
• T-Lymphocytes (drug effects)