Event Title

Reprogramming of Veins Into Arteries for Cardiac Bypass Surgery

Session Number

P06

Advisor(s)

Kishore Wary, University of Illinois at Chicago

Location

B-206 Lecture Hall

Start Date

28-4-2016 9:15 AM

End Date

28-4-2016 9:40 AM

Disciplines

Medicine and Health Sciences

Abstract

For coronary bypass surgery, the great saphenous vein is routinely used as a replacement graft. However, the venous graft often fails primarily due to “cellular mismatch,” as venous endothelial cells (ECs) have never seen oxygenated arterial blood before. Therefore, prior to grafting, reprogramming of venous ECs to arterial identity provides a clinically relevant approach to enhance graft patency and reduce the prevalence of graft failure. Cultured human saphenous vein ECs (hSapVECs) were treated with chromatin- modifying chemicals (5-Azacytidine, 5-Aza and Trichostatin A, TSA) and Wnt3a. To determine conversion to arterial fate, total RNA was prepared and subjected to qRT-PCR to amplify arteriovenous- specific genes. Treated hSapVECs showed significant increases in the expression of arterial genes and dramatic decreases in venous genes in a dose-dependent manner, indicating the ability of 5-Aza, TSA, and Wnt signaling to diminish venous identity and thereby induce arterial phenotype. Furthermore, microscopic examination of hSapVECs treated identically showed robust induction in the level of critical arterial-specific proteins. Importantly, this stimulation in an ex vivo experiment also induced robust neovascularization. We demonstrate that venous ECs can be epigenetically reprogrammed into arterial ECs. Thus, altering the venous ECs to arterial fate prior to grafting should minimize “cellular mismatch,” thereby increasing the chance of a successful saphenous vein graft.


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Apr 28th, 9:15 AM Apr 28th, 9:40 AM

Reprogramming of Veins Into Arteries for Cardiac Bypass Surgery

B-206 Lecture Hall

For coronary bypass surgery, the great saphenous vein is routinely used as a replacement graft. However, the venous graft often fails primarily due to “cellular mismatch,” as venous endothelial cells (ECs) have never seen oxygenated arterial blood before. Therefore, prior to grafting, reprogramming of venous ECs to arterial identity provides a clinically relevant approach to enhance graft patency and reduce the prevalence of graft failure. Cultured human saphenous vein ECs (hSapVECs) were treated with chromatin- modifying chemicals (5-Azacytidine, 5-Aza and Trichostatin A, TSA) and Wnt3a. To determine conversion to arterial fate, total RNA was prepared and subjected to qRT-PCR to amplify arteriovenous- specific genes. Treated hSapVECs showed significant increases in the expression of arterial genes and dramatic decreases in venous genes in a dose-dependent manner, indicating the ability of 5-Aza, TSA, and Wnt signaling to diminish venous identity and thereby induce arterial phenotype. Furthermore, microscopic examination of hSapVECs treated identically showed robust induction in the level of critical arterial-specific proteins. Importantly, this stimulation in an ex vivo experiment also induced robust neovascularization. We demonstrate that venous ECs can be epigenetically reprogrammed into arterial ECs. Thus, altering the venous ECs to arterial fate prior to grafting should minimize “cellular mismatch,” thereby increasing the chance of a successful saphenous vein graft.