Systemic Succinate, Hypoxia-Inducible Factor-1 Alpha, and IL-1β Gene Expression in Autosomal Dominant Polycystic Kidney Disease with and without Hypertension.
Adult
Cell Hypoxia
/ genetics
Cross-Sectional Studies
Female
Gene Expression
/ physiology
Humans
Hypertension
/ blood
Hypoxia-Inducible Factor 1, alpha Subunit
/ genetics
Interleukin-1beta
/ genetics
Male
Middle Aged
Nephritis
/ genetics
Polycystic Kidney, Autosomal Dominant
/ blood
RNA, Messenger
/ metabolism
Renin-Angiotensin System
/ genetics
Hypertension
Hypoxia-inducible factor-1 alpha
Polycystic kidney disease
Succinate
Journal
Cardiorenal medicine
ISSN: 1664-5502
Titre abrégé: Cardiorenal Med
Pays: Switzerland
ID NLM: 101554863
Informations de publication
Date de publication:
2019
2019
Historique:
received:
06
01
2019
accepted:
09
04
2019
pubmed:
19
7
2019
medline:
7
7
2020
entrez:
19
7
2019
Statut:
ppublish
Résumé
Cyst pressure induces renin-angiotensin-aldosterone system activation and kidney hypoxia in autosomal dominant polycystic kidney disease (ADPKD). Lipopolysaccharide-induced Toll-like receptor activation causes metabolic disturbances that are triggered by increased succinate levels and hypoxia inducible factors, which results in inflammation via IL-1β activation. Since we aimed to investigate the role of both inflammation and hypoxia in the clinical course of ADPKD, via succinate levels from sera samples, HIF-1α gene expression from whole blood and urine samples and IL-1βgene expression from whole blood were measured. One hundred ADPKD patients and 100 matched healthy controls were enrolled to this cross-sectional study. Twenty-four-hour ambulatory blood pressure monitoring was conducted in all participants. Blood, serum, and urine samples were taken after 12-h fasting for the measurement of biochemical parameters and succinate levels. Whole blood and urine samples were used for HIF-1α and IL-1β geneexpression by using quantitative real-time PCR. There were significant differences in whole blood HIF-1α, IL-1β geneexpression, and serumsuccinate levels between the ADPKD patients and the control subjects. Whole blood HIF-1αgene expression, IL-1β geneexpression, and serumsuccinate levels were also significantly different in ADPKD patients with hypertension in comparison with normotensive ones (p < 0.05). Serum succinate levels and blood IL-1β geneexpression were increased in ADPKD patients with high levels of HIF-1α geneexpression (p = 0.018 and p = 0.029, respectively). Increased age,low eGFR, and HIF-1α and IL-1β geneexpressions were also independently associated with hypertension in ADPKD patients. Inflammation and hypoxia are both relevant factors that might be associated with hypertension in ADPKD.
Sections du résumé
BACKGROUND AND OBJECTIVES
Cyst pressure induces renin-angiotensin-aldosterone system activation and kidney hypoxia in autosomal dominant polycystic kidney disease (ADPKD). Lipopolysaccharide-induced Toll-like receptor activation causes metabolic disturbances that are triggered by increased succinate levels and hypoxia inducible factors, which results in inflammation via IL-1β activation. Since we aimed to investigate the role of both inflammation and hypoxia in the clinical course of ADPKD, via succinate levels from sera samples, HIF-1α gene expression from whole blood and urine samples and IL-1βgene expression from whole blood were measured.
METHODS
One hundred ADPKD patients and 100 matched healthy controls were enrolled to this cross-sectional study. Twenty-four-hour ambulatory blood pressure monitoring was conducted in all participants. Blood, serum, and urine samples were taken after 12-h fasting for the measurement of biochemical parameters and succinate levels. Whole blood and urine samples were used for HIF-1α and IL-1β geneexpression by using quantitative real-time PCR.
RESULTS
There were significant differences in whole blood HIF-1α, IL-1β geneexpression, and serumsuccinate levels between the ADPKD patients and the control subjects. Whole blood HIF-1αgene expression, IL-1β geneexpression, and serumsuccinate levels were also significantly different in ADPKD patients with hypertension in comparison with normotensive ones (p < 0.05). Serum succinate levels and blood IL-1β geneexpression were increased in ADPKD patients with high levels of HIF-1α geneexpression (p = 0.018 and p = 0.029, respectively).
CONCLUSIONS
Increased age,low eGFR, and HIF-1α and IL-1β geneexpressions were also independently associated with hypertension in ADPKD patients. Inflammation and hypoxia are both relevant factors that might be associated with hypertension in ADPKD.
Identifiants
pubmed: 31319406
pii: 000500478
doi: 10.1159/000500478
doi:
Substances chimiques
HIF1A protein, human
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
IL1B protein, human
0
Interleukin-1beta
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
370-381Informations de copyright
© 2019 S. Karger AG, Basel.