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Microbiota-governed microRNA-204 impairs endothelial function and blood pressure decline during inactivity in db/db mice
Journal article   Open access   Peer reviewed

Microbiota-governed microRNA-204 impairs endothelial function and blood pressure decline during inactivity in db/db mice

Ravinder Reddy Gaddam, Veronica Peotta Jacobsen, Young-Rae Kim, Mohanad Gabani, Julia S. Jacobs, Karishma Dhuri, Santosh Kumar, Modar Kassan, Qiuxia Li, Raman Bahal, …
Scientific reports, Vol.10(1), pp.10065-10065
06/22/2020
DOI: 10.1038/s41598-020-66786-0
PMCID: PMC7308358
PMID: 32572127
url
https://doi.org/10.1038/s41598-020-66786-0View
Published (Version of record) Open Access

Abstract

An impaired decline in blood pressure at rest is typical in people with diabetes, reflects endothelial dysfunction, and increases the risk of end-organ damage. Here we report that microRNA-204 (miR-204) promotes endothelial dysfunction and impairment in blood pressure decline during inactivity. We show that db/db mice overexpress miR-204 in the aorta, and its absence rescues endothelial dysfunction and impaired blood pressure decline during inactivity despite obesity. The vascular miR-204 is sensitive to microbiota, and microbial suppression reversibly decreases aortic miR-204 and improves endothelial function, while the endothelial function of mice lacking miR-204 remained indifferent to the microbial alterations. We also show that the circulating miR-122 regulates vascular miR-204 as miR-122 inhibition decreases miR-204 in endothelial cells and aorta. This study establishes that miR-204 impairs endothelial function, promotes impairment in blood pressure decline during rest, and opens avenues for miR-204 inhibition strategies against vascular dysfunction.
Cardiovascular biology miRNAs

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