Upregulation of epidermal gap junctional proteins in patients with venous disease

M. Kanapathy, R. Simpson, L. Madden, C. Thrasivoulou, A. Mosahebi, D. L. Becker, T. Richards

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Leg ulceration is a feared complication of venous insufficiency. It is not known whether varicose veins predispose skin to poor wound healing. The expression pattern of gap junctional protein connexin, a known marker of poor wound healing, was investigated across various stages of venous disease. Methods: Patients undergoing intervention for varicose veins were assessed according to the Clinical Etiologic Anatomic Pathophysiologic (CEAP) classification of varicose veins. Paired 4-mm punch biopsies were taken from above the ankle (pathological) and above the knee (control). Tissues were stained with haematoxylin and eosin, and for connexin 43, connexin 30 and connexin 26. Results: Forty-eight paired biopsies were taken (12 each for CEAP class C0, C2, C4 and C6). The pathological skin showed progressive epithelial hyperthickening, an increase in the number and depth of rete ridges, increased inflammation and loss of dermal architecture with disease progression from C4 onwards. The overall absolute connexin expression and mean connexin expression per cell in the pathological skin similarly increased across the CEAP classes from as early as C2. Increasing levels of connexin in control skin were also noted, indicating progression of the disease proximally. Connexin 43 expression showed the strongest positive correlation between pathological and control skin. Conclusion: Connexins were overexpressed in patients with simple varicose veins, with a stepwise increased expression through venous eczema to ulceration. Connexin 43 is a potential biomarker for venous disease. This finding suggests that varicose veins predispose skin to poor wound healing. Surgical relevance The overexpression of connexins, a family of gap junctional proteins, is known to cause poor healing in venous leg ulceration. It is not known whether there is any association with superficial venous disease. Here, connexin proteins were overexpressed in patients with uncomplicated varicose veins, before histological skin changes. Connexin could be a biomarker of venous disease progression.

Original languageEnglish
Pages (from-to)59-67
Number of pages9
JournalBritish Journal of Surgery
Volume105
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018
Externally publishedYes

Fingerprint

Connexins
Up-Regulation
Varicose Veins
Skin
Connexin 43
Proteins
Wound Healing
Disease Progression
Leg
Biomarkers
Biopsy
Venous Insufficiency
Eczema
Hematoxylin
Eosine Yellowish-(YS)
Ankle
Knee
Inflammation

Cite this

Kanapathy, M., Simpson, R., Madden, L., Thrasivoulou, C., Mosahebi, A., Becker, D. L., & Richards, T. (2018). Upregulation of epidermal gap junctional proteins in patients with venous disease. British Journal of Surgery, 105(1), 59-67. https://doi.org/10.1002/bjs.10653
Kanapathy, M. ; Simpson, R. ; Madden, L. ; Thrasivoulou, C. ; Mosahebi, A. ; Becker, D. L. ; Richards, T. / Upregulation of epidermal gap junctional proteins in patients with venous disease. In: British Journal of Surgery. 2018 ; Vol. 105, No. 1. pp. 59-67.
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Kanapathy, M, Simpson, R, Madden, L, Thrasivoulou, C, Mosahebi, A, Becker, DL & Richards, T 2018, 'Upregulation of epidermal gap junctional proteins in patients with venous disease' British Journal of Surgery, vol. 105, no. 1, pp. 59-67. https://doi.org/10.1002/bjs.10653

Upregulation of epidermal gap junctional proteins in patients with venous disease. / Kanapathy, M.; Simpson, R.; Madden, L.; Thrasivoulou, C.; Mosahebi, A.; Becker, D. L.; Richards, T.

In: British Journal of Surgery, Vol. 105, No. 1, 01.01.2018, p. 59-67.

Research output: Contribution to journalArticle

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Kanapathy M, Simpson R, Madden L, Thrasivoulou C, Mosahebi A, Becker DL et al. Upregulation of epidermal gap junctional proteins in patients with venous disease. British Journal of Surgery. 2018 Jan 1;105(1):59-67. https://doi.org/10.1002/bjs.10653