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.

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