Transplantation-induced endothelial dysfunction as studied in rat aorta allografts

E Andriambeloson, C Pally, B Hengerer… - …, 2001 - journals.lww.com
E Andriambeloson, C Pally, B Hengerer, C Cannet, Z Nikolova, C Bruns, HG Zerwes…
Transplantation, 2001journals.lww.com
Background. Clinical evidence indicates that vascular endothelial cell (EC) dysfunction
occurs early after transplantation (Tx) and initiates chronic graft vasculopathy. This study
explored this phenomenon in rat aorta Tx using the stringent Dark Agouti (DA)-to-Lewis
(LEW) and the weak Fischer 344 (F344)-to-LEW strain combinations. Methods. Donor
abdominal aortae were orthotopically grafted into LEW rats. At post-Tx days 7, 14, 28, and
56, grafts were collected to assess changes in EC morphology (en face silver staining) and …
Abstract
Background.
Clinical evidence indicates that vascular endothelial cell (EC) dysfunction occurs early after transplantation (Tx) and initiates chronic graft vasculopathy. This study explored this phenomenon in rat aorta Tx using the stringent Dark Agouti (DA)-to-Lewis (LEW) and the weak Fischer 344 (F344)-to-LEW strain combinations.
Methods.
Donor abdominal aortae were orthotopically grafted into LEW rats. At post-Tx days 7, 14, 28, and 56, grafts were collected to assess changes in EC morphology (en face silver staining) and EC function, ie, vasodilatory response to acetylcholine (ACH) after phenylephrine (PHE) precontraction; changes in vascular smooth muscle cell (VSMC) α-actin (western blotting), degree of apoptosis (caspase-3 activity), and morphology.
Results.
In DA allografts, VSMC and EC dysfunctions developed concomitantly and were completed at 14 days post-Tx, most likely due to the EC and α-actin-positive VSMC loss. Meanwhile, allografts revealed markedly increased caspase-3 activity. Neointima formation, restricted to the edges of allografts at day 28, covered the entire allografts by day 56 post-Tx.
Lippincott Williams & Wilkins