Polyester vascular patches acquire arterial or venous identity depending on their environment

Abstract

Polyester is commonly used in vascular surgery for patch angioplasty and grafts. We hypothesized that polyester patches heal by infiltration of arterial or venous progenitor cells depending on the site of implantation. Polyester patches were implanted into the Wistar rat aorta or inferior vena cava and explanted on day 7 or 30. Neointima that formed on polyester patches was thicker in the venous environment compared to the amount that formed on patches in the arterial environment. Venous patches had more cell proliferation and greater numbers of VCAM-positive and CD68-positive cells, whereas arterial patches had greater numbers of vimentin-positive and alpha-actin-positive cells. Although there were similar numbers of endothelial progenitor cells in the neointimal endothelium, cells in the arterial patch were Ephrin-B2- and notch-4-positive while those in the venous patch were Eph-B4- and COUP-TFII-positive. Venous patches treated with an arteriovenous fistula had decreased neointimal thickness; neointimal endothelial cells expressed Ephrin-B2 and notch-4 in addition to Eph-B4 and COUP-TFII. Polyester patches in the venous environment acquire venous identity, whereas patches in the arterial environment acquire arterial identity; patches in the fistula environment acquire dual arterial-venous identity. These data suggest that synthetic patches heal by acquisition of identity of their environment.

Inhibition of programmed death‐1 decreases neointimal hyperplasia after patch angioplasty

“…9,10 Previously we showed that lymphocytes and macrophages accumulate in the neointima that forms on the luminal surface after patch angioplasty. 11,12 We also showed that lymphocytes and macrophages are present in the nascent neointima of a human vein graft. 13 Furthermore, macrophages and T cells induce neointimal hyperplasia in a mouse carotid artery injury model, 14,15 whereas depleting macrophages inhibits neointimal hyperplasia in a rabbit balloon injury model 16 ; we also showed that nanoparticles containing rapamycin that were conjugated to the pericardial patch decrease neointimal thickness and macrophage accumulation.…”

Pathophysiologic Role of Molecules Determining Arteriovenous Differentiation in Adult Life

“…Interestingly, in a rat model of polyester patches implanted into the aorta or inferior vena cava, polyester patches healed by infiltration of host arterial or venous progenitor cells depending on the site of implantation. Moreover, when these synthetic patches were treated with AVF, they would have decreased neointimal thickness with neointimal ECs expressing the arterial identity markers ephrin-B2 and Notch4, in addition to the venous identity markers Eph-B4 and COUP-TFII (dual arterial-venous identity) [60]. These data suggest that synthetic patches heal by acquisition of identity of their environment.…”

Molecular identity of arteries, veins, and lymphatics

“…Venous patches additionally exposed to arterial flow also gain arterial identity, that is they gain dual arterial-venous identity, similar to arteriovenous fistulae ( Table II ). 10,12 These changes in identity occur in synthetic patches, suggesting that host cells infiltrating into the vascular patch determine vessel identity in these models. 12 It is interesting to speculate that manipulation of vascular patch identity may be possible, and if so, this may be a strategy to inhibit local development of neointimal hyperplasia.…”