Long-term endothelial dysfunction in irradiated vessels: an immunohistochemical analysis

Area of Science:

• Vascular Surgery
• Oncologic Surgery
• Reconstructive Surgery

Background:

• Microvascular free flap reconstruction is standard for head and neck defects.
• Pre-operative radiotherapy increases free flap malperfusion and revision rates.
• Irradiated vessels exhibit histomorphological and structural changes, with incompletely understood long-term endothelial dysfunction.

Purpose of the Study:

• To investigate long-term endothelial dysfunction in irradiated arteries.
• To analyze the expression of adhesion molecules, selectins, eNOS, thrombomodulin, and PAI-1 in irradiated versus non-irradiated arteries.

Main Methods:

• Immunohistochemistry and Remmele scale grading were used to analyze endothelial expression.
• Markers assessed included ICAM-1, VCAM-1, E-selectin, P-selectin, eNOS, thrombomodulin, and PAI-1.
• The average radiation dose was 58.7 Gy, with tissue sampling occurring 106 months post-radiation.

Main Results:

• Irradiated arteries showed significantly increased expression of ICAM-1, VCAM-1, E-selectin, P-selectin, and PAI-1 compared to non-irradiated controls.
• While thrombomodulin and eNOS expression showed no difference in the initial comparison, eNOS was significantly lower in irradiated vessels when comparing within individuals.
• Irradiated vessels demonstrated higher expression of ICAM-1, VCAM-1, E-/p-Selectin, and PAI-1.

Conclusions:

• Irradiated arteries exhibit persistent endothelial dysfunction with elevated pro-thrombotic and pro-inflammatory markers years after radiotherapy.
• This ongoing endothelial dysfunction contributes to complications in microvascular free flap reconstructions.
• Targeting endothelial dysfunction in irradiated vessels could potentially reduce complication rates.