M S Whiteley1, S J Dos Santos2, T J Fernandez-Hart3, C T D Lee4, J M Li5. 1. The Whiteley Clinic, Stirling House, Stirling Road, Guildford, Surrey GU2 7RF, UK; University of Surrey, Faculty of Health and Medical Sciences, Guildford, Surrey GU2 7TE, UK. Electronic address: mark@thewhiteleyclinic.co.uk. 2. The Whiteley Clinic, Stirling House, Stirling Road, Guildford, Surrey GU2 7RF, UK; University of Surrey, Faculty of Health and Medical Sciences, Guildford, Surrey GU2 7TE, UK. 3. The Whiteley Clinic, Stirling House, Stirling Road, Guildford, Surrey GU2 7RF, UK. 4. University of Surrey, Faculty of Health and Medical Sciences, Guildford, Surrey GU2 7TE, UK. 5. University of Reading, Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, Reading, Berkshire RG6 6AS, UK.
Abstract
OBJECTIVE/ BACKGROUND: Traditionally, sclerotherapy has been thought to work by the cytotoxic effect of the sclerosant upon the endothelium alone. However, studies have shown that sclerotherapy is more successful in smaller veins than in larger veins. This could be explained by the penetration of the sclerosant, or its effect, into the media. This study aimed to investigate intimal and medial damage profiles after sclerosant treatment. METHODS: Fresh human varicose veins were treated ex vivo with either 1% or 3% sodium tetradecyl sulphate (STS) for 1 or 10 minutes. The effect of the sclerosant on the vein wall was investigated by immunofluorescent labelling of transverse vein sections using markers for endothelium (CD31), smooth muscle (α-actin), apoptosis (p53) and inflammation (intercellular adhesion molecule-1 [ICAM-1]). Polidocanol (POL; 3%) treatment at 10 minutes was similarly investigated. RESULTS: Endothelial cell death was concentration- and time-dependent for STS but incomplete for both sclerosants. Time, but not concentration, significantly affected cell death (p > .001). A 40% and 30% maximum reduction was observed for STS and POL, respectively. Destruction of 20-30% of smooth muscle cells was found up to 250 μm from the lumen after 3% STS treatment for 10 minutes. POL treatment for 10 minutes showed inferior destruction of medial cells. Following STS treatment and 24-hour tissue culture, p53 and ICAM-1 were upregulated to a depth of around 300 μm. This effect was not observed with POL. CONCLUSION: Inflammatory and apoptotic markers show the same distribution as medial cell death, implying that sclerotherapy with STS works by inducing apoptosis in the vein wall rather than having an effect restricted to the endothelium. Incomplete loss of endothelial cells and penetration of the sclerosant effect up to 250 μm into the media suggest that medial damage is crucial to the success of sclerotherapy and may explain why it is less effective in larger veins.
OBJECTIVE/ BACKGROUND: Traditionally, sclerotherapy has been thought to work by the cytotoxic effect of the sclerosant upon the endothelium alone. However, studies have shown that sclerotherapy is more successful in smaller veins than in larger veins. This could be explained by the penetration of the sclerosant, or its effect, into the media. This study aimed to investigate intimal and medial damage profiles after sclerosant treatment. METHODS: Fresh human varicose veins were treated ex vivo with either 1% or 3% sodium tetradecyl sulphate (STS) for 1 or 10 minutes. The effect of the sclerosant on the vein wall was investigated by immunofluorescent labelling of transverse vein sections using markers for endothelium (CD31), smooth muscle (α-actin), apoptosis (p53) and inflammation (intercellular adhesion molecule-1 [ICAM-1]). Polidocanol (POL; 3%) treatment at 10 minutes was similarly investigated. RESULTS: Endothelial cell death was concentration- and time-dependent for STS but incomplete for both sclerosants. Time, but not concentration, significantly affected cell death (p > .001). A 40% and 30% maximum reduction was observed for STS and POL, respectively. Destruction of 20-30% of smooth muscle cells was found up to 250 μm from the lumen after 3% STS treatment for 10 minutes. POL treatment for 10 minutes showed inferior destruction of medial cells. Following STS treatment and 24-hour tissue culture, p53 and ICAM-1 were upregulated to a depth of around 300 μm. This effect was not observed with POL. CONCLUSION: Inflammatory and apoptotic markers show the same distribution as medial cell death, implying that sclerotherapy with STS works by inducing apoptosis in the vein wall rather than having an effect restricted to the endothelium. Incomplete loss of endothelial cells and penetration of the sclerosant effect up to 250 μm into the media suggest that medial damage is crucial to the success of sclerotherapy and may explain why it is less effective in larger veins.
Authors: Elisabetta Bottaro; Jemma A J Paterson; Luciano Quercia; Xunli Zhang; Martyn Hill; Venisha A Patel; Stephen A Jones; Andrew L Lewis; Timothy M Millar; Dario Carugo Journal: Sci Rep Date: 2019-07-08 Impact factor: 4.379