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Updated: Dec 13, 2025

Procedure for Human Saphenous Veins Ex Vivo Perfusion and External Reinforcement
Published on: October 1, 2014
Mechanism of thromboxane receptor-induced vasoconstriction in human saphenous vein
Gulsev Ozen1, Khadija Aljesri1, Zeynep Celik1
1Department of Pharmacology, Faculty of Pharmacy, Istanbul University, Istanbul 34116, Turkey.
Insights
Thromboxane A2 (TXA2) causes saphenous vein (SV) vasoconstriction via calcium influx and Rho-kinase. This mechanism impairs vasorelaxation, potentially explaining SV graft failure in coronary artery bypass graft surgery.
Area of Science:
- Vascular Biology
- Pharmacology
- Cardiovascular Surgery
Background:
- Saphenous vein (SV) is a primary graft in coronary artery bypass graft (CABG) surgery.
- Thromboxane A2 (TXA2) contributes to SV graft failure through vasoconstriction and platelet aggregation.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying TXA2-induced vasoconstriction in human SV.
- To investigate the impact of TXA2-mediated contraction on SV vasorelaxation.
Main Methods:
- Isolated organ bath system to assess vasoconstriction.
- U46619 (TXA2-mimetic) used for pre-contraction.
- Evaluation of various inhibitors and blockers (ML-9, BAY u3405, U73122, calphostin C, Y-27632, nifedipine, SKF96365).
- Assessment of relaxation responses to NO donors, PDE inhibitors, AC activators, and acetylcholine.
Main Results:
- U46619-induced contraction is blocked by ML-9 and BAY u3405.
- Contraction involves extracellular calcium influx (L-type and store-operated channels), intracellular calcium release, and Rho-kinase activation.
- Vasorelaxation to SNP, riociguat, sildenafil, IBMX, forskolin, and ACh is significantly reduced in U46619-pre-contracted SV.
- Evidence of crosstalk between TP receptor signaling and PDE, AC, GC pathways.
Conclusions:
- TXA2-induced vasoconstriction in human SV is mediated by calcium influx, release, and Rho-kinase-dependent sensitization.
- TXA2 significantly impairs SV vasorelaxation, suggesting a role in graft dysfunction.
- Understanding these mechanisms offers targets for preventing SV graft failure in CABG patients.
Abstract:
Saphenous vein (SV) is one of the most widely used graft material in patients undergoing coronary artery bypass graft surgery (CABG). Thromboxane A2 (TXA2) is implicated in graft failure by inducing vasoconstriction and platelet aggregation. The aim of this study is to investigate the mechanism involved in TXA2-induced vasoconstriction in human SV. The role of different inhibitors and blockers on U46619 (TXA2-mimetic)-induced vasoconstriction is investigated by using an isolated organ bath system. Relaxation responses to several mediators are evaluated in SV pre-contracted with U46619 and compared with those pre-contracted with phenylephrine. Our results demonstrate that U46619-induced contraction is completely blocked by myosin light chain kinase inhibitor ML-9 or TP receptor antagonist BAY u3405. Furthermore, U46619-induced contraction is partially inhibited by phospholipase C inhibitor U73122, protein kinase C inhibitor calphostin C, Rho-kinase inhibitor Y-27632, L-type calcium channel blocker nifedipine, store-operated channel inhibitor SKF96365 or removal of extracellular calcium. Relaxation responses to NO donor (sodium nitroprusside), guanylate cyclase (GC) stimulator (riociguat), phosphodiesterase (PDE) inhibitors (sildenafil, IBMX), adenylate cyclase (AC) activator (forskolin) and acetylcholine (ACh) are markedly reduced when U46619 is used as a pre-contraction agent. Our results demonstrate that influx of extracellular Ca2+ (through L-type calcium channels and store-operated calcium channels) and intracellular Ca2+ release together with Ca2+ sensitization (through Rho-kinase activation) are necessary components for TXA2-induced vasoconstriction in SV. Moreover, more pronounced decrease in vasorelaxation induced by several mediators (SNP, riociguat, sildenafil, IBMX, forskolin, and ACh) in the presence of U46619 when compared with phenylephrine suggests that there is a crosstalk between the TP receptor signaling pathway and PDE, AC, GC enzymes. We believe that the investigation of mechanism of the TXA2-induced vasoconstriction in SV will provide additional information for the prevention of SV graft failure.
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