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Gut microbiota contributes to the development of hypertension in a genetic mouse model of systemic lupus erythematosus
Author(s) -
Visitación Néstor,
RoblesVera Iñaki,
Toral Marta,
GómezGuzmán Manuel,
Sánchez Manuel,
Moleón Javier,
GonzálezCorrea Cristina,
MartínMorales Natividad,
O'Valle Francisco,
Jiménez Rosario,
Romero Miguel,
Duarte Juan
Publication year - 2021
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.15512
Subject(s) - immunology , gut flora , systemic lupus erythematosus , biology , medicine , genetics , pathology , disease
Background and Purpose Hypertension is an important cardiovascular risk factor that is prevalent in the systemic lupus erythematosus patient population. Here, we have investigated whether intestinal microbiota is involved in hypertension in a genetic mouse model of systemic lupus erythematosus. Experimental Approach Twenty‐six‐week‐old female NZW/LacJ (control) and NZBWF1 (F1 hybrid of New Zealand Black and New Zealand White strains; systemic lupus erythematosus) mice were treated for 6 weeks with a broad‐spectrum antibiotic mixture or with vancomycin. Faecal microbiota transplantation was performed from donor systemic lupus erythematosus group to recipient to germ‐depleted or germ‐free mice. Key Results Antibiotic treatment inhibited the development of hypertension and renal injury, improved endothelial dysfunction and vascular oxidative stress, and decreased aortic Th17 infiltration in NZBWF1 mice. High BP and vascular complications found in systemic lupus erythematosus mice, but not autoimmunity, kidney inflammation and endotoxemia, were reproduced by the transfer of gut microbiota from systemic lupus erythematosus donors to germ‐free or germ‐depleted mice. Increased proportions of Bacteroides were linked with high BP in these mice. The reduced endothelium‐dependent vasodilator responses to acetylcholine and the high BP induced by microbiota from hypertensive systemic lupus erythematosus mice were inhibited after IL‐17 neutralization. Conclusion and Implications Changes in T‐cell populations, endothelial function, vascular inflammation and hypertension driven by a genetic systemic lupus erythematosus background can be modified by antibiotic‐induced changes in gut microbiota. The vascular changes induced by hypertensive systemic lupus erythematosus microbiota were mediated by Th17 infiltration in the vasculature.

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