MicroRNA-425 and microRNA-155 cooperatively regulate atrial natriuretic peptide expression and cGMP production.

PLoS One
Authors
Keywords
Abstract

AIMS: Atrial natriuretic peptide (ANP), secreted primarily by atrial cardiomyocytes, decreases blood pressure by raising cyclic 3',5'-guanosine monophosphate (cGMP) levels and inducing vasorelaxation, natriuresis, and diuresis. Raising the level of ANP has been shown to be an effective treatment for hypertension. To advance the future development of an anti-microRNA (miR) approach to increasing expression of ANP, we investigated the regulation of NPPA expression by two miRs: miR-425 and miR-155. We examined whether miR-425 and miR-155 have an additive effect on the expression and function of ANP.

METHODS AND RESULTS: Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) were transfected with miR-425, miR-155, or a combination of the two miRs. Two days later, NPPA expression was measured using real time qPCR. Each of the miRs decreased NPPA expression over a wide range of concentrations, with a significant reduction at concentrations as low as 1 nM. The combination of miR-425 and miR-155 reduced NPPA expression to a greater extent than either miR-425 or miR-155 alone. An in vitro assay was developed to study the potential biological significance of the miR-induced decrease in NPPA expression. The cooperative effect of miR-425 and miR-155 on NPPA expression was associated with a significant decrease in cGMP levels.

CONCLUSIONS: These data demonstrate that miR-425 and miR-155 regulate NPPA expression in a cooperative manner. Targeting both miRNAs with anti-miRs (possibly at submaximal concentrations) might prove to be a more effective strategy to modulate ANP levels, and thus blood pressure, than targeting either miRNA alone.

Year of Publication
2018
Journal
PLoS One
Volume
13
Issue
4
Pages
e0196697
Date Published
2018
ISSN
1932-6203
DOI
10.1371/journal.pone.0196697
PubMed ID
29698509
PubMed Central ID
PMC5919659
Links
Grant list
R01 HL130391 / HL / NHLBI NIH HHS / United States
R01 HL124262 / HL / NHLBI NIH HHS / United States
R01HL113933 / NH / NIH HHS / United States
DK082971 / NH / NIH HHS / United States
R01 DK082971 / DK / NIDDK NIH HHS / United States
R01HL124262 / NH / NIH HHS / United States
R01 HL113933 / HL / NHLBI NIH HHS / United States