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Systemic Succinate, Hypoxia-Inducible Factor-1 Alpha, and IL-1β Gene Expression in Autosomal Dominant Polycystic Kidney Disease with and without Hypertension.
- Source :
-
Cardiorenal medicine [Cardiorenal Med] 2019; Vol. 9 (6), pp. 370-381. Date of Electronic Publication: 2019 Jul 18. - Publication Year :
- 2019
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Abstract
- 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.<br />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.<br />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).<br />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.<br /> (© 2019 S. Karger AG, Basel.)
- Subjects :
- 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
Polycystic Kidney, Autosomal Dominant complications
RNA, Messenger metabolism
Renin-Angiotensin System genetics
Hypertension complications
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Interleukin-1beta metabolism
Polycystic Kidney, Autosomal Dominant genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1664-5502
- Volume :
- 9
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cardiorenal medicine
- Publication Type :
- Academic Journal
- Accession number :
- 31319406
- Full Text :
- https://doi.org/10.1159/000500478