Kidney Week

Abstract: SA-PO786

Role of Platelet-Derived Growth Factor (PDGF) in Ex Vivo Aortic Calcification Under Uremic Conditions

Session Information

• Hypertension and CVD: Mechanisms
  November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1503 Hypertension and CVD: Mechanisms

Authors

• Yesilyurt, Burcu, Rheinisch-Westfalische Technische Hochschule Aachen, Aachen, Nordrhein-Westfalen, Germany

Burcu Yesilyurt,

• Zhang, Li, Universitatsklinikum Aachen, Aachen, Nordrhein-Westfalen, Germany

Li Zhang,

• Klinkhammer, Barbara Mara, Universitatsklinikum Aachen, Aachen, Nordrhein-Westfalen, Germany

Barbara Mara Klinkhammer,

• Moellmann, Julia, Universitatsklinikum Aachen, Aachen, Nordrhein-Westfalen, Germany

Julia Moellmann,

• Droste, Patrick, Universitatsklinikum Aachen, Aachen, Nordrhein-Westfalen, Germany

Patrick Droste,

• Goettsch, Claudia, Universitatsklinikum Aachen, Aachen, Nordrhein-Westfalen, Germany

Claudia Goettsch,

• Jahnen-Dechent, Willi, Universitatsklinikum Aachen, Aachen, Nordrhein-Westfalen, Germany

Willi Jahnen-Dechent,

• Lehrke, Michael, Universitatsklinikum Aachen, Aachen, Nordrhein-Westfalen, Germany

Michael Lehrke,

• Hohl, Mathias, Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes, Homburg, Saarland, Germany

Mathias Hohl,

• Jankowski, Joachim, Rheinisch-Westfalische Technische Hochschule Aachen, Aachen, Nordrhein-Westfalen, Germany

Joachim Jankowski,

• Wong, Dickson WL, Universitatsklinikum Aachen, Aachen, Nordrhein-Westfalen, Germany

Dickson WL Wong,

• Boor, Peter, Universitatsklinikum Aachen, Aachen, Nordrhein-Westfalen, Germany

Peter Boor,

Background

Chronic kidney disease (CKD) is associated with an increased risk of developing vascular calcification. Platelet-derived growth factor (PDGF) is involved in vascular development and vasculopathy via effects on vascular smooth muscle cells (VSMCs). It remains unclear whether PDGF might be involved in CKD-associated vascular calcification.

Methods

To address this, we adapted an ex-vivo calcification model in murine aortas to analyze the effect of uremia and PDGF. We first examined whether aortic calcification is affected by age, sex, genetic background, incubation time-points of calcification medium (3-10days), and various aortic regions (arch, thoracic, suprarenal and infrarenal). Aortas collected from control and CKD mice (induced by an adenine-enriched diet) were calcified ex-vivo to examine the effect of CKD conditioning on calcification. Hemodialysate from CKD patients was added to the calcification medium to create the uremic milieu ex-vivo. Soluble PDGFR-β antibody and Imatinib were used as an inhibitor of PDGFR-β. Ex-vivo calcification was also performed on the transgenic aorta with tamoxifen-inducible activation of PDGFR-β specifically in VSMCs.

Results

With these approaches, we observed that longer (10days) incubation in the calcification medium led to an increased calcification in all aortic regions. Aortas from older mice had higher susceptibility to calcify ex-vivo, whereas sex and genetic background had no effects. Aortas from CKD mice calcified significantly more than those of healthy mice. Similarly, adding hemodialysate to the calcification medium enhanced calcification, which was significantly diminished upon PDGF signaling inhibition. Additionally, aortas from mice with constitutive PDGFR-β activation in VSMCs showed a higher calcification compared to WT mice.

Conclusion

Overall, our results suggested that PDGFR-β activation in VSMCs is involved in uremic vascular calcification.

Funding

• Private Foundation Support