Increased expression of hypoxia-inducible factor-1alpha and Bcl-2 in varicocele and varicose veins

Primary vein wall abnormalities leading to secondary blood stasis and increased venous pressure that cause tissue hypoxia are observed in varicocele and varicose veins. Both types of diseased vessels are characterized by dilated thickened vein walls. Hypoxia upregulates Bcl-2 (antiapoptosis protein) expression in different human cell types. We studied the expression of hypoxia-inducible factor-1alpha (HIF-1α) and Bcl-2 in both venous diseases.

All vascular specimens, including the saphenous and internal spermatic veins, from patients with either varicocele or left inguinal herniorrhaphy (control group) were studied using immunoblotting, immunohistochemical staining, and double immunofluorescence staining. The data were analyzed using 1-way analysis of variance with Tukey comparison test.

Protein analysis revealed that both venous diseases had a higher expression of HIF-1α and Bcl-2 compared with the control group (P < 0.05). Immunohistochemical staining and double immunofluorescence staining revealed that the greatest degree of HIF-1α and Bcl-2 colocalization occurred in the muscle layer of both diseased vessels. Moreover, under confocal microscopy, elevated Bcl-2 expression was found in the endothelium of both study groups compared with the control group.

Our findings revealed increased expression of HIF-1α and Bcl-2 in varicocele and varicose veins and increased Bcl-2 expression especially in the endothelium under hypoxia. Thus, Bcl-2 overexpression may protect cells against apoptosis and contribute to the dilated thickened walls seen in both types of diseased vessels.