Smooth Muscle Cell Hypertrophy in Varicose Veins Is Associated with Expression of Estrogen Receptor-β

Abstract

Varicose veins are characterized by dilated and thickened vein walls. This study examined whether the changes that occur in varicose veins are associated with smooth muscle cell (SMC) hypertrophy, cellular proliferation or apoptosis. Moreover, the association between SMC hypertrophy and the expression of the estrogen receptor-β (ERβ) was investigated. Varicose veins were obtained from male patients during vascular stripping surgery (n = 11) and nonvaricose veins during coronary bypass surgery, also from male subjects (n = 12). The cellular volume of the SMC in both the longitudinal and circular layer of the vessel wall was measured using stereological methods. Apoptosis was detected using the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling) technique. SMC proliferation and ERβ expression were investigated by immunohistochemistry. Neither in the longitudinal nor in the circular layer of the varicose vein wall were signs of apoptosis or proliferation present. However, the mean cellular volume of the SMC in the circular layer of the varicose veins was strongly increased (5,291 ± 363 µm³) as compared to non-varicose veins (2,812 ± 212 µm³, p < 0.001). Moreover, ERβ expression in the circular layer of varicose veins (63 ± 4%) significantly differed from nonvaricose veins (39 ± 4%; p = 0.001). Interestingly, the SMC volume correlated with ERβ expression (r = 0.71, p < 0.001). These data show that cell death or proliferation of SMC do not, or only rarely, occur in varicose veins. However, remodeling of varicose veins can mainly be attributed to increased volumes of the SMC of the circular layer and this increase correlates with ERβ expression.