Pathogenic mechanisms in varicose vein disease: the role of hypoxia and inflammation

Aims: Although the aetiology of varicose veins remains unknown, recent studies have focused on endothelial cell integrity and function. Among the regulatory factors of vessel tone, synthesises, pro- and anti-inflammatory, adhesion molecules and the transcription factor hypoxia inducible factor-1 alpha (HIF-1 alpha), which are responsible for recruiting leukocytes, are very important. Methods: Investigation in this study focused on the expression of ICAM-1, E-selectin and HIF-1 alpha on endothelial cells using immunostaining and RT-PCR in varicose vein specimens compared with controls. Results: Findings of this study showed alterations of the intima, such as focal intimal discontinuity and denudation of endothelium in varicose veins. Based on data derived from immunostaining and RT-PCR, no major differences were identified between ICAM-1 and E-selectin expression in varicose vein specimens compared with controls. In contrast, immunostaining results identified HIF-1 alpha expression in five (5/20) varicose vein specimens, whereas no control saphenous vein specimens expressed HIF-1 alpha. Conclusions: These findings could explain other evidence of hypoxia in varicose veins. Finally, results already obtained in this investigation suggest that the process of pathogenesis of varicose veins is not restricted to the role of adhesion molecules.