High endogenous estradiol is associated with increased venous distensibility and clinical evidence of varicose veins in menopausal women

Ciardullo, Anna V.; Panico, Salvatore; Bellati, Cristina; Rubba, P.; Rinaldi, Sabina; Iannuzzi, Arcangelo; Cioffi, Vincenzo; Iannuzzo, Gabriella; Berrino, Franco

doi:10.1067/mva.2000.107768

Cited by 51 publications

(45 citation statements)

References 25 publications

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“…No association was found for sex hormonebinding globulin or testosterone. 7,8 Several lines of evidence also support a role for sex steroid hormones in the pathogenesis of varicose veins in men. An elevated serum estradiol/testosterone ratio was found in men with primary varicose veins compared with healthy controls.…”

mentioning

confidence: 94%

Elevated sex steroid hormones in great saphenous veins in men

Kendler

Makrantonaki

Kratzsch

et al. 2010

Journal of Vascular Surgery

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Elevated serum estradiol and testosterone levels were detected in men with varicose veins and reflux in the GSV compared with the patient's own arm veins. Enzymes and hormonal receptors involved in steroid metabolism were down-regulated in patients with GSV reflux and varicose veins, suggestive of a negative feedback regulation. These data support the notion of a possible causal relationship between sex steroids and varicose veins in men.

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mentioning

confidence: 94%

Elevated sex steroid hormones in great saphenous veins in men

Kendler

Makrantonaki

Kratzsch

et al. 2010

Journal of Vascular Surgery

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“…Though compelling evidence has elucidated the role of estrogen in vascular protection, elevated estrogen levels have been shown to be associated with vascular remodeling and varicose veins (25,26). In addition, VSMC proliferation and migration play important roles in vascular reforming (27). Therefore, we hypothesized that estrogen may directly influence the physiological function of VSMCs.…”

Section: Resultsmentioning

confidence: 99%

“…However, increasing numbers of risk factors, such as hormonal changes, obesity, leg injury, prolonged standing, a highly refined diet and tight undergarments have been reported to be involved in the development of this disease (8,25,26). Hormonal changes, such as elevated estrogen levels, which occur during pregnancy, have been reported to play a major role in the development of varicose veins (27). Alterations in hormonal levels inducing hypertrophy and the growth of the SMC layer in varicose veins have been suggested in different studies (28)(29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

IQGAP1 modulates the proliferation and migration of vascular smooth muscle cells in response to estrogen

Huang

Jin

Zhou

et al. 2015

International Journal of Molecular Medicine

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Abstract. Vascular smooth muscle cell (VSMC) proliferation and migration has been proven to be a critical event in the development of varicosity. Variations in estrogen levels, a pathological event related to age and pregnancy, play a role in the pathogenesis of varicosity. Previous studies have reported a different response of VSMCs following estrogen stimulation. However, the exact mechanisms involved have not yet been elucidated. In the present study, we examined the responses of lesion and normal VSMCs treated with 10 -8 M 17β-estradiol (E 2 ) for 24 h. A differential effect of exposure to E 2 was observed in these cells. IQ-domain GTPase-activating protein 1 (IQGAP1), a scaffold protein, was overexpressed in the lesion VSMCs and was shown to modulate VSMC proliferation and migration in response to E 2 . Furthermore, the increased expression of IQGAP1 was found to be intimately associated with a high activity of estrogen receptor α (ERα), which has been implicated in the regulation of VSMC physiological function. Additionally, we found that two critical kinases, Akt and extracellular signal-regulated kinase (ERK), mediated the activation of ERα and VSMC proliferation. According to our results, we thus concluded that high levels of IQGAP1 in VSMCs regulate the physiological reaction of the cells in response to estrogen exposure, and that kinases are involved in the process by mediating ERα activation. In view of the essential role of IQGAP1 in the physiological function of VSMCs, targeting this molecule may prove to be a promising strategy for the treatment of varicosity.

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“…As the venous wall is a key component of Virchow's triad required for the initiation of the thrombus ), more work is needed to understand how various estrogenic products affect both the endothelium and smooth muscle of veins to develop products with arterial protection but limited venous risks. Varicose veins represent a venous disorder that is associated with increases in circulating estrogen (Vin et al, 1992;Ciardullo et al, 2000). However, causality of this condition is complicated by various genetic components and physical factors such as obesity.…”

Section: Veinsmentioning

confidence: 99%