Effekte der Barorezeptoraktivierungstherapie auf Marker des Endoplasmatischen Retikulum Stresses
Effects of baroreflex activation therapy on marker of endoplasmic reticulum stress
by Kathrin Anina Schierke
Date of Examination:2019-11-12
Date of issue:2019-11-04
Advisor:Prof. Dr. Michael Koziolek
Referee:Prof. Dr. Michael Koziolek
Referee:Prof. Dr. Marco Schroeter
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Abstract
English
Introduction: Arterial hypertension is present in 30-45% of the adult population and represents a significant public health problem. Although hypertension is one of the major risk factors for the high rate of cardiovascular events and progression of renal disease, blood pressure targets are often not reached. Accumulating evidence suggests the involvement of sympathetic overactivity in the development of hypertension. Baroreflex activation therapy (BAT) is a new therapy option in the treatment of resistant hypertension which affects 20-30% of the hypertensive population. Electrical stimulation of baroreceptors attenuates the activity of the sympathetic nervous system and augments parasympathetic activity, thus reducing blood pressure. Recent evidence shows that endoplasmic reticulum stress (ER stress) is involved in a diverse range of diseases such as diabetes, renal failure and hypertension. The aim of this project was to assess ER stress in patients with resistant hypertension by analysing protein markers of ER stress (endoplasmic reticulum stress protein 57 (ERp57), glucose-regulated protein 78 (GRP78) and calreticulin). Methods: A total of 29 patients with resistant hypertension receiving BAT and 17 healthy individuals (control group) were included in this study. Spot urine and serum samples were collected at baseline and after 6 months of BAT. The urinary and serum concentration of ER stress proteins was measured by western blot analysis and enzyme-linked immunosorbent assay (ELISA). Results: At 6 month follow-up both systolic (from 172 ± 27 mmHg to 154 ± 29 mmHg) and diastolic (from 89 ± 18 mmHg to 82 ± 19 mmHg) office blood pressure was significantly reduced (all p < 0,01). After 6 month of therapy GRP78 serum levels (1433 ng/ml) were significantly higher (p < 0,0002) compared with those at baseline (1119,9 ng/ml). Calreticulin and ERp57 levels did not change significantly. Conclusion: This study demonstrates that BAT was not associated with a significant change of ER stress levels accept for GRP78 serum levels. Whether chronic baroreceptor stimulation has favorable renoprotective effects (e. g. by reducing ER stress) beyond the blood pressure lowering effect should be investigated in further projects. Studying ER stress in hypertensive patients could help in the long term to develop new therapeutic strategies (e. g. by modulating ER stress) and to identify novel biomarkers for disease activity.
Keywords: hypertension; baroreceptor activation therapy; endoplasmic reticulum stress; ERp57; calreticulin; GRP78