Deficiency of MicroRNA-181a Results in Transcriptome-Wide Cell-Specific Changes in the Kidney and Increases Blood Pressure

MicroRNA miR-181a is downregulated in the kidneys of hypertensive patients and hypertensive mice. In vitro, miR-181a is a posttranslational inhibitor of renin expression, but pleiotropic mechanisms by which miR-181a may influence blood pressure (BP) are unknown. Here, we determined whether deletion...

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Veröffentlicht in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2021-11, Vol.78 (5), p.1322-1334
Hauptverfasser: Paterson, Madeleine R., Jackson, Kristy L., Dona, Malathi S.I., Farrugia, Gabriella E., Visniauskas, Bruna, Watson, Anna M.D., Johnson, Chad, Prieto, Minolfa C., Evans, Roger G., Charchar, Fadi J., Pinto, Alexander R., Marques, Francine Z., Head, Geoffrey A.
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Sprache:eng
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Zusammenfassung:MicroRNA miR-181a is downregulated in the kidneys of hypertensive patients and hypertensive mice. In vitro, miR-181a is a posttranslational inhibitor of renin expression, but pleiotropic mechanisms by which miR-181a may influence blood pressure (BP) are unknown. Here, we determined whether deletion of miR-181a/b-1 in vivo changes BP and the molecular mechanisms involved at the single-cell level. We developed a KO (knockout) mouse model lacking miR-181a/b-1 genes using CRISPR/Cas9 technology. Radiotelemetry probes were implanted in 12-week-old C57BL/6J WT (wild type) and miR-181a/b-1 KO mice. Systolic and diastolic BP were 4- to 5-mm Hg higher in KO compared with WT mice over 24 hours (P
ISSN:0194-911X
1524-4563
DOI:10.1161/HYPERTENSIONAHA.121.17384