Obesity-induced hypertension. The role of PXR-4βHC-LXR axis, a novel regulatory pathway
Thesis event information
Date and time of the thesis defence
Place of the thesis defence
Auditorium F202 (Aapistie 5B), Kontinkangas campus
Topic of the dissertation
Obesity-induced hypertension. The role of PXR-4βHC-LXR axis, a novel regulatory pathway
Doctoral candidate
Licentiate of Medicine (M.D.) Roosa Rahunen
Faculty and unit
University of Oulu Graduate School, Faculty of Medicine, Research Unit of Biomedicine and Internal Medicine
Subject of study
Medicine, internal medicine
Opponent
Professor Teemu Niiranen, University of Turku
Custos
Professor Janne Hukkanen, University of Oulu
Obesity-induced hypertension
Hypertension affects 30% of the world’s population, and is a major risk factor for cardiovascular diseases. Overweight and obesity are also major global health issues. The coexistence of hypertension and overweight/obesity is common, since it is established that blood pressure (BP) increases as body weight increases. However, the mechanisms underlying the pathophysiology of obesity-induced hypertension are not completely understood.
This thesis investigated the role of pregnane X receptor (PXR) activation in BP regulation, as well as the role of PXR-regulated 4β-hydroxycholesterol (4βHC) as a BP-lowering factor. In addition, the prognostic significance of 4βHC in coronary artery disease was evaluated.
Administration of the PXR-activating antibiotic rifampicin significantly increased BP in healthy volunteers (n=62). In turn, rifampicin increased the levels of plasma 4βHC and an inverse association was detected between 4βHC and BP. Similar results were found in experimental animals, since PXR activation increased BP and elevated 4βHC levels appeared to decrease BP. Also, an inverse association was detected between 4βHC and body mass index (BMI).
The associations between 4βHC, BMI and BP were also explored in a larger study population (n=645) and the differences between men and women were evaluated. Similar inverse associations between 4βHC and BP, as well as between 4βHC and BMI, were observed. Plasma 4βHC levels predicted BP levels, particularly in women.
In addition the prognostic role of 4βHC was examined in coronary artery disease patients during an 8.8-year follow-up. The subjects who had the highest 4βHC levels at baseline were generally healthier based on traditional factors, but surprisingly the men in this population faced the highest incidence of sudden cardiac death.
This thesis provides new information on the role of PXR and PXR-regulated 4βHC in BP regulation. These findings may contribute to the development of new treatment strategies for obesity-induced hypertension. In addition, plasma 4βHC levels may have prognostic value in men with coronary artery disease.
This thesis investigated the role of pregnane X receptor (PXR) activation in BP regulation, as well as the role of PXR-regulated 4β-hydroxycholesterol (4βHC) as a BP-lowering factor. In addition, the prognostic significance of 4βHC in coronary artery disease was evaluated.
Administration of the PXR-activating antibiotic rifampicin significantly increased BP in healthy volunteers (n=62). In turn, rifampicin increased the levels of plasma 4βHC and an inverse association was detected between 4βHC and BP. Similar results were found in experimental animals, since PXR activation increased BP and elevated 4βHC levels appeared to decrease BP. Also, an inverse association was detected between 4βHC and body mass index (BMI).
The associations between 4βHC, BMI and BP were also explored in a larger study population (n=645) and the differences between men and women were evaluated. Similar inverse associations between 4βHC and BP, as well as between 4βHC and BMI, were observed. Plasma 4βHC levels predicted BP levels, particularly in women.
In addition the prognostic role of 4βHC was examined in coronary artery disease patients during an 8.8-year follow-up. The subjects who had the highest 4βHC levels at baseline were generally healthier based on traditional factors, but surprisingly the men in this population faced the highest incidence of sudden cardiac death.
This thesis provides new information on the role of PXR and PXR-regulated 4βHC in BP regulation. These findings may contribute to the development of new treatment strategies for obesity-induced hypertension. In addition, plasma 4βHC levels may have prognostic value in men with coronary artery disease.
Created 8.5.2026 | Updated 8.5.2026