Kidney Week

Abstract: TH-PO218

Serum-Derived Exosomes from Patients on Dialysis Promote Endothelial-Mesenchymal Transition and Vascular Calcification

Session Information

• Hypertension and CVD: Basic Research Findings
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1601 Hypertension and CVD: Basic

Authors

• Cohen-Hagai, Keren, Meir Medical Center, Kfar Saba, Central, Israel

Keren Cohen-Hagai, MD

• Kuchuk, Eran, Meir Medical Center, Kfar Saba, Central, Israel

Eran Kuchuk, MD

• Tartakover Matalon, Shelly, Meir Medical Center, Kfar Saba, Central, Israel

Shelly Tartakover Matalon, PhD

• Benchetrit, Sydney, Meir Medical Center, Kfar Saba, Central, Israel

Sydney Benchetrit, MD

• Zitman Gal, Tali, Meir Medical Center, Kfar Saba, Central, Israel

Tali Zitman Gal, PhD

Background

Vascular calcifications (VC) is prevalent among dialysis patients and associate with Cardiovasculare events (CVE).
Exosomes, small extracellular vesicles secreted by cells, are mediators of cell-cell interactions and are also involved in biological processes such as apoptosis and inflammation.
Endothelial-Mesenchymal Transition (EndMT) has been observed in pathological conditions involving vascular damage and inflammation. Bone morphogenetic protein (BMP) associates with CVE and vascular inflammation. BMPs and the RUNX2 transcription factor are able to stimulate osteoblast differentiation and bone formation.
We aimed to assess the effect of serum derived exosomes on EndMT and VC markers

Methods

Serum samples from Twenty dialysis patients with confirmed VC and 10 healthy volunteers were taken at dialysis initiation for exosome isolation.
Human umbilical vein endothelial cells (HUVECs) were treated with 100 µg/mL exosomes for 24-96 hours. At the end of incubation, cells were collected for mRNA and protein analysis.

Results

VC exosomes induced EndMT in HUVECs; after 24h, a decrease in endothelial markers CD31 and VE-cadherin vs. healthy exosomes (↓ 31% and ↓51%, respectively; P<0.001) N-cadherin and Vimentin vs. healthy exosomes (↑156% and ↑ 283%, respectively; P<0.001). These two cytokines upregulated the expression of Snail (↑153% ;P=0.03). After 96h of incubation, expression of genes essential for osteoblast differentiation that include bone morphogenetic genes (BMP2, BMPR2, BMP4 and BMP9), as well as the transcription factor RUNX2 were significantly elevated.

Conclusion

Exosomes derived from dialysis patients' serum induced EndMT and contributed to calcification