Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Ganss, P.
Targeting bone sialoprotein (BSP) in an experimental
model of uremic medial calcification
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2024. pp.
- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Eller Kathrin
- Schuller Max
- Altmetrics:
- Abstract:
- Introduction: High phosphate levels are a typical consequence of advanced stages of chronic kidney disease (CKD). Phosphate triggers the transdifferentiation of vascular smooth muscle cells (VSMCs) of the tunica media of vessel walls to an osteoblastic phenotype. This goes along with a down-regulation of calcification inhibitors and an increase in calcification promotors like bone sialoprotein (BSP) and collagen type I is increased, which leads to a change in the composition of the extracellular matrix within the tunica media. BSP has a key role in formation of hydroxyapatite crystals as it serves as nucleation site for these crystals, which are subsequently embedded in the tunica media of the vessel wall. This results in medial calcification with complications such as isolated systolic hypertension, decreased perfusion of coronary arteries and damage to the microvasculature, especially in kidneys and in the central nervous system. In the present study, we investigated the application of anti-BSP-antibodies as potential therapeutic option for uremic medial calcification. Materials and Methods: Five groups with ten female DBA2/N mice each received four intraperitoneal injections of the respective antibody of vehicle each over a period of 16 days. Three groups were treated with the monoclonal antibody FP21 in different concentrations (0.4 mg/mL, 1.2 mg/mL, 3.6 mg/mL). The remaining two groups served as control groups. One group was treated with phosphate-buffered saline (PBS) and the other one with the reference antibody IDK-1. IDK-1 is a rat monoclonal anti-BSP-antibody, which should not show any effect in mice. On day 8, diet was changed from standard chow to a high-phosphate diet. This diet contained 20.2 g of phosphorus, 9.4 g of calcium, 0.7 g of magnesium, and 500 IU/kg of vitamin D3 per kilogram. After eight days of high-phosphate diet, calcium content of kidneys, hearts and abdominal aortas was determined as well as concentration of blood urea nitrogen (BUN). Furthermore, histological staining of calcium deposits with Alizarin Red of heart and kidney samples was performed. Results: Histological staining of kidney and heart samples, as well as the determination of calcium content of kidney, heart and abdominal aortas did not show significant differences between the groups. Similarly, BUN levels as a marker for kidney function were comparable between the groups. Discussion: Our results did not show any effect of the anti-BSP antibody FP21 on the investigated outcomes in our high-phosphate model. Furthermore, our study focused on “hard” outcome parameters and potential alteration of VSMC phenotype was not examined. A major limitation was the severity of this model, which did not allow a longer duration of treatment. The application of FP21 in a modified animal model could be further investigated.