Circulating let-7g-5p and miR-191-5p Are Independent Predictors of Chronic Kidney Disease in Hypertensive Patients.
Adult
Aged
Albuminuria
/ blood
Blood Pressure
Case-Control Studies
Circulating MicroRNA
/ blood
Down-Regulation
Female
Glomerular Filtration Rate
Humans
Hypertension
/ blood
Kidney
/ physiopathology
Male
MicroRNAs
/ blood
Middle Aged
Predictive Value of Tests
Prognosis
Renal Insufficiency, Chronic
/ blood
biomarker
blood pressure
hypertension
microRNA
target organ damage
Journal
American journal of hypertension
ISSN: 1941-7225
Titre abrégé: Am J Hypertens
Pays: United States
ID NLM: 8803676
Informations de publication
Date de publication:
21 05 2020
21 05 2020
Historique:
received:
16
10
2019
revised:
15
12
2019
accepted:
25
02
2020
pubmed:
3
3
2020
medline:
22
12
2020
entrez:
3
3
2020
Statut:
ppublish
Résumé
Hypertension (HTN) is associated with target organ damage such as cardiac, vascular, and kidney injury. Several studies have investigated circulating microRNAs (miRNAs) as biomarkers of cardiovascular disease, but few have examined them as biomarker of target organ damage in HTN. We aimed to identify circulating miRNAs that could serve as biomarkers of HTN-induced target organ damage using an unbiased approach. Fifteen normotensive subjects, 16 patients with HTN, 15 with HTN associated with other features of the metabolic syndrome (MetS), and 16 with HTN or chronic kidney disease (CKD) were studied. Circulating RNA extracted from platelet-poor plasma was used for small RNA sequencing. Differentially expressed (DE) genes were identified with a threshold of false discovery rate <0.1. DE miRNAs were identified uniquely associated with HTN, MetS, or CKD. However, only 2 downregulated DE miRNAs (let-7g-5p and miR-191-5p) could be validated by reverse transcription-quantitative PCR. Let-7g-5p was associated with large vessel stiffening, miR-191-5p with MetS, and both miRNAs with estimated glomerular filtration rate (eGFR) and neutrophil and lymphocyte fraction or number and neutrophil-to-lymphocyte ratio. Using the whole population, stepwise multiple linear regression generated a model showing that let-7g-5p, miR-191-5p, and urinary albumin/creatinine ratio predicted eGFR with an adjusted R2 of 0.46 (P = 8.5e-7). We identified decreased circulating let-7g-5p and miR-191-5p as independent biomarkers of CKD among patients with HTN, which could have pathophysiological and therapeutic implications.
Sections du résumé
BACKGROUND
Hypertension (HTN) is associated with target organ damage such as cardiac, vascular, and kidney injury. Several studies have investigated circulating microRNAs (miRNAs) as biomarkers of cardiovascular disease, but few have examined them as biomarker of target organ damage in HTN. We aimed to identify circulating miRNAs that could serve as biomarkers of HTN-induced target organ damage using an unbiased approach.
METHODS AND RESULTS
Fifteen normotensive subjects, 16 patients with HTN, 15 with HTN associated with other features of the metabolic syndrome (MetS), and 16 with HTN or chronic kidney disease (CKD) were studied. Circulating RNA extracted from platelet-poor plasma was used for small RNA sequencing. Differentially expressed (DE) genes were identified with a threshold of false discovery rate <0.1. DE miRNAs were identified uniquely associated with HTN, MetS, or CKD. However, only 2 downregulated DE miRNAs (let-7g-5p and miR-191-5p) could be validated by reverse transcription-quantitative PCR. Let-7g-5p was associated with large vessel stiffening, miR-191-5p with MetS, and both miRNAs with estimated glomerular filtration rate (eGFR) and neutrophil and lymphocyte fraction or number and neutrophil-to-lymphocyte ratio. Using the whole population, stepwise multiple linear regression generated a model showing that let-7g-5p, miR-191-5p, and urinary albumin/creatinine ratio predicted eGFR with an adjusted R2 of 0.46 (P = 8.5e-7).
CONCLUSIONS
We identified decreased circulating let-7g-5p and miR-191-5p as independent biomarkers of CKD among patients with HTN, which could have pathophysiological and therapeutic implications.
Identifiants
pubmed: 32115655
pii: 5770956
doi: 10.1093/ajh/hpaa031
pmc: PMC7241936
doi:
Substances chimiques
Circulating MicroRNA
0
MIRN191 microRNA, human
0
MicroRNAs
0
mirnlet7 microRNA, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
505-513Subventions
Organisme : CIHR
Pays : Canada
Informations de copyright
© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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