Abstract: FR-PO705
Endothelial-to-Mesenchymal Transition in Neointimal Hyperplasia of a Mice Model of Arteriovenous Fistula
Session Information
- Dialysis: Vascular Access - I
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 704 Dialysis: Vascular Access
Author
- Liu, Chung-te, Division of Internal Medicine, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan
Background
To date, arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. However, for the matured AVF, the 2-year patency without intervention was only 30-50%. In addition, frequent interventional procedures were required to maintain AVF patency, which causes immense suffer to patients. As such, medical treatment to prevent AVF stenosis is desired.
Stenosis of AVF resulted from the process of neointimal hyperplasia, signifying thickening of subintima caused by proliferation of cells express α-smooth muscle actin (α-SMA) and vimentin. The pathogenic role of neointimal hyperplasia in AVF stenosis has been confirmed by multiple studies, however, understanding of its molecular mechanism is still suboptimal.
Endothelial-to-mesenchymal transition (EndMT) is the process that endothelial cells transform to mesenchymal cells, which had been demonstrated in pathogenic fibrogenesis of cardiovascular diseases. This study tries to demonstrate EndMT in a mice AVF model.
Methods
Chronic kidney disease (CKD) in mice is induced by diet containing 0.2% adenine. After 10 days of adenine diet, CKD was confirmed by elevated serum creatinine and surgical creation of AVF was performed.
Murine AVF model is created by aortocaval puncture to form AVF between abdominal aorta and inferior vena cava (IVC). The successful creation of AVF was confirmed by doppler ultrasound during surgery. Six weeks after AVF creation, the mice were sacrificed and AVF was resected. The specimens were stained for α-SMA and vascular endothelial-cadherin (VE-cadherin) to show the expression of both endothelial and mesenchymal features of the proliferated intima.
Results
After 10 days of adenine containing diet, serum creatinine increased significantly from 0.25 mg/dL to 0.73 mg/dL. Immediately after AF creation, doppler ultrasound showed increased blood flow and exaggerated pulsation wave form of the IVC proximal to AVF site. The IVC wall adjacent to AVF site showed proliferated intima, which stains positive for α-SMA. Co-staining the same area showed that the proliferated intima expressed both α-SMA and VE-cadherin, which indicated possible EndMT.
Conclusion
This pilot study provided preliminary evidence of the presence of EndMT in AVF mice model, which may underly the pathogenic stenosis of human AVF. However, more evidence is still required to confirm EndMT in AVF and its molecular pathway.