Estrogen and progesterone receptors in normal and varicose saphenous veins

Mashiah, A; Berman, V.; Thole, Hubert; Rose, Sam; Pasik, S; Schwarz, Henry; Ben‐Hur, Herzl

doi:10.1016/s0967-2109(98)00132-x

Cited by 54 publications

(48 citation statements)

References 16 publications

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“…The volume of SMC in the circular layer of varicose veins correlated with the expression of ER ␤ . The increase in ER ␤ expression in varicose veins confi rms the study of Mashiah et al [22] who related this fi nding to gender differences. However, since in the present study only a male population was involved, other explanations such as biochemical alterations should be taken into account.…”

Section: Discussionsupporting

confidence: 85%

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

Knaapen¹,

Somers²,

Bortier³

et al. 2005

J Vasc Res

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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.

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Section: Discussionsupporting

confidence: 85%

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

Knaapen¹,

Somers²,

Bortier³

et al. 2005

J Vasc Res

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“…In view of the presence of estrogen receptor in the coronary arteries and the expression of estrogen and progesterone receptors in the normal and varicose GSV, it seems that the sex steroids, especially estrogens, may directly regulate the growth, differentiation and function of the cells in the vascular system [25,31,32]. In this study, the effect of gender may be included in the statistical analysis.…”

Section: Discussionmentioning

confidence: 97%

Collagen alteration in vascular remodeling by hemodynamic factors

et al. 2000

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The collagen alterations in the vascular wall remodeled by hemodynamic change were investigated by electron microscopy and immunohistochemistry. The left anterior descending coronary artery (LAD) without a myocardial bridge (MB) showed both lower matrix metalloproteinase-1 (MMP-1) expression and a smaller extent of spiraled collagen (SC) distribution than the LAD wall with MB, in which the intima was influenced by high shear stress. In the wall of the varicose great saphenous vein (GSV) the expression of MMP-1 was lower, while the expression of prolyl 4-hydroxylase was higher, than in the normal GSV. The extent of SC distribution in the intima and media of the varicose GSV was smaller than that in the normal GSV. An analogous difference in results was demonstrated between the portal vein (PV) of patients with liver cirrhosis and normal PV. However, the levels of expression of MMP-2, MMP-9 and tissue inhibitors of MMP (TIMPs) in these pathologic vessels were not different from those in the corresponding normal vessels. The results indicate that hemodynamic forces such as shear stress and increased intravascular blood pressure contribute to the collagen alterations in the vascular wall, which may lead to vascular wall remodeling.

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“…CVI is associated with increased expression of estrogen and progesterone receptors in the wall of varicose veins in females [22] . In contrast, we did not reveal any gender-related difference in the TGF-␤ signaling pathway in the vein wall.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Transforming Growth Factor-β Signaling Pathway in the Wall of Normal and Varicose Veins

Kowalewski

Małkowski²,

Sobolewski³

et al. 2010

Pathobiology

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Objective(s): Extracellular matrix remodeling in the vein wall is involved in varicose vein pathogenesis, with transforming growth factor β₁ (TGF-β₁) playing a potential role. The aim of the study was to assess the TGF-β signaling pathway including its receptor (TGF-β RII) and phosphorylated receptor-regulated Smads (p-Smad2/3) in varicose veins. Methods: Varicose veins from patients undergoing varicose vein surgery were the studied material, whereas normal greater saphenous veins from patients undergoing infrainguinal arterial bypass surgery were the control material. Expression of TGF-β RII mRNA was assessed with RT-PCR, whereas expression of TGF-β RII and p-Smad2/3 proteins was assessed with Western blot. Results: A significantly increased TGF-β RII mRNA level was found in varicose veins (287 ± 24%), when compared with normal veins (100 ± 26%). The receptor protein expression reflected a changed mRNA level with significantly increased TGF-β RII protein in varicose veins (290 ± 21%), when compared with controls (100 ± 16%). Enhanced TGF-β RII expression was accompanied by increased p-Smad2/3 protein expression in varicose veins (257 ± 19%) in comparison with normal veins (100 ± 9%). Conclusion(s): Increased TGF-β RII expression and activation in the wall of varicose veins may be involved in extracellular matrix remodeling related to TGF-β₁ and supports its role in the disease pathogenesis.

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Estrogen and progesterone receptors in normal and varicose saphenous veins

Cited by 54 publications

References 16 publications

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

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

Collagen alteration in vascular remodeling by hemodynamic factors

Evaluation of Transforming Growth Factor-β Signaling Pathway in the Wall of Normal and Varicose Veins

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