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Orthotopic Aortic Transplantation: A Rat Model to Study the Development of Chronic Vasculopathy
Published on: December 4, 2010
Transplantation-induced endothelial dysfunction as studied in rat aorta allografts
E Andriambeloson1, C Pally, B Hengerer
1Transplantation Research, Novartis Pharma AG, Basel, Switzerland.
Transplantation
|January 5, 2002
Summary
Vascular endothelial cell dysfunction in rat aorta transplants precedes graft vasculopathy. The F344-to-LEW model effectively studies this early endothelial cell dysfunction after transplantation.
Area of Science:
- Transplantation immunology
- Vascular biology
- Organ transplant research
Background:
- Vascular endothelial cell (EC) dysfunction is an early event in transplantation (Tx), initiating chronic graft vasculopathy.
- This study investigates EC dysfunction in rat aorta Tx using stringent (DA-to-LEW) and weak (F344-to-LEW) strain combinations.
Purpose of the Study:
- To explore the early onset and progression of EC dysfunction and vasculopathy in rat aorta allografts.
- To compare the development of these changes between different donor-recipient strain combinations.
Main Methods:
- Rat aorta allografts were created and analyzed at multiple time points post-Tx (days 7, 14, 28, 56).
- Assessed EC morphology and function, vascular smooth muscle cell (VSMC) alpha-actin expression, apoptosis (caspase-3 activity), and neointima formation.
Main Results:
- DA allografts showed early EC and VSMC dysfunction, increased apoptosis, and neointima formation by day 56.
- F344 allografts exhibited reduced vasodilatory response by day 7, with no EC denudation but leukocyte adhesion; neointima formed by day 56.
Conclusions:
- Transplant-induced EC dysfunction precedes vasculopathy in rat aorta allografts.
- The F344-to-LEW strain combination is optimal for studying early EC dysfunction post-transplantation.
