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Systemic Succinate, Hypoxia-Inducible Factor-1 Alpha, and IL-1β Gene Expression in Autosomal Dominant Polycystic
Ismail Kocyigit1, Serpil Taheri2, Eray Eroglu3
1Department of Nephrology, Erciyes University Medical Faculty, Kayseri, Turkey, iikocyigit@gmail.com.
Insights
Inflammation and hypoxia, indicated by succinate levels and gene expression, are linked to hypertension in autosomal dominant polycystic kidney disease (ADPKD). These factors, including hypoxia-inducible factor-1α (HIF-1α) and interleukin-1β (IL-1β), are elevated in ADPKD patients, especially those with hypertension.
Area of Science:
- Nephrology
- Molecular Biology
- Cardiovascular Research
Background:
- Autosomal dominant polycystic kidney disease (ADPKD) involves cyst pressure, renin-angiotensin-aldosterone system activation, and kidney hypoxia.
- Inflammation, triggered by lipopolysaccharide-induced Toll-like receptor activation, metabolic disturbances, increased succinate, and hypoxia-inducible factors (HIFs), plays a role in ADPKD pathogenesis via IL-1β activation.
Purpose of the Study:
- To investigate the roles of inflammation and hypoxia in the clinical course of ADPKD.
- To measure succinate levels, HIF-1α gene expression, and IL-1β gene expression in ADPKD patients.
Main Methods:
- A cross-sectional study involving 100 ADPKD patients and 100 healthy controls.
- 24-h ambulatory blood pressure monitoring, biochemical parameter analysis, and measurement of serum succinate levels.
- Quantitative real-time PCR was used to measure whole blood and urine HIF-1α and IL-1β gene expression.
Main Results:
- Significant differences in whole blood HIF-1α, IL-1β gene expression, and serum succinate levels were observed between ADPKD patients and controls.
- Hypertension in ADPKD patients was associated with significantly higher HIF-1α, IL-1β gene expression, and serum succinate levels compared to normotensive ADPKD patients.
- Serum succinate and IL-1β gene expression were elevated in ADPKD patients with high HIF-1α gene expression.
Conclusions:
- Increased age, reduced estimated glomerular filtration rate (eGFR), and elevated HIF-1α and IL-1β gene expression are independently associated with hypertension in ADPKD.
- Inflammation and hypoxia are key factors potentially associated with hypertension in ADPKD patients.
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.
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