Media Damage Following Detergent Sclerotherapy Appears to be Secondary to the Induction of Inflammation and Apoptosis: An Immunohistochemical Study Elucidating Previous Histological Observations

Whiteley, Mark S; Santos, Scott J Dos; Fernandez-Hart, Tim J; Lee, C. T. D.; Li, Jian-Mei

doi:10.1016/j.ejvs.2015.11.011

Cited by 41 publications

(27 citation statements)

References 24 publications

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“…Recent studies by Whiteley et al, [2] demonstrated an apoptotic effect of detergent sclerosants in endothelial and smooth muscle cells (SMC) of the endothelium and media from varicose veins. While this work showed that sclerosants increase apoptosis on areas where endothelial markers were decreased, the results were limited to the expression of just one apoptotic marker (p53) by fluorescence microscopy.…”

Section: Discussionmentioning

confidence: 99%

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Detergent sclerosants at sub-lytic concentrations induce endothelial cell apoptosis through a caspase dependent pathway

et al. 2016

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To investigate the apoptotic effects of detergent sclerosants sodium tetradecylsulphate (STS) and polidocanol (POL) on endothelial cells at sub-lytic concentrations. Human umbilical vein endothelial cells (HUVECs) were isolated and labelled with antibodies to assess for apoptosis and examined with confocal microscopy and flow cytometry. Isolated HUVECs viability was assessed using propidium iodide staining. Early apoptosis was determined by increased phosphatidylserine exposure by lactadherin binding. Caspase 3, 8, 9 and Bax activation as well as inhibitory assays with Pan Caspase (Z-VAD-FMK) and Bax (BI-6C9) were assessed to identify apoptotic pathways. Porimin activation was used to assess cell membrane permeability. Cell lysis reached almost 100 % with STS at 0.3 % and with POL at 0.6 %. Apoptosis was seen with both STS and POL at concentrations ranging from 0.075 to 0.15 %. PS exposure increased with both STS and POL and exhibited a dose-dependent trend. Active Caspase 3, 8 and 9 but not Bax were increased in HUVECs stimulated with low concentrations of both STS and POL. Inhibitory assays demonstrated Caspase 3, 8, 9 inhibition at low concentrations (0.075 to 0.6 %) with both STS and POL. Both agents increased the activation of porimin at all concentrations. Both sclerosants induced endothelial cell (EC) apoptosis at sub-lytic concentrations through a caspase-dependant pathway. Both agents induced EC oncosis.

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Section: Discussionmentioning

confidence: 99%

“…The lytic effect on the endothelial cells (EC) results in exposure of the underlying collagen leading to endovascular fibrosis and occlusion. Although in recent years the mechanism of action of detergent sclerosants has been explored more in depth [1,2], the mechanism by which cell death results is currently unknown.…”

Section: Introductionmentioning

confidence: 99%

Detergent sclerosants at sub-lytic concentrations induce endothelial cell apoptosis through a caspase dependent pathway

et al. 2016

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“…Following recent findings regarding sclerotherapy, apoptosis has been proposed as a cell death mechanism after thermal ablation. 6 The objective of this study was to analyse the biological effects of a 1920 nm EVL on an ex vivo large tributary bypassing a hypoplastic segment of the GSV, often called an “extra-fascial GSV,” treated in vitro , by histology and immunofluorescence.…”

Section: Objectivesmentioning

confidence: 99%

Histological and Immunofluorescent Analysis of a Large Tributary of the Great Saphenous Vein Treated with a 1920 nm Endovenous Laser: Preliminary Findings

Ashpitel

Dabbs

Nemchand

et al. 2018

EJVES Short Reports

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ObjectivesTo analyse the biological effects of a 1920 nm endovenous laser (EVL) on extra-fascial great saphenous vein (GSV) in vitro.MethodsA 10 cm length of a large tributary bypassing a hypoplastic segment of the GSV (sometimes called an “extra-fascial GSV”) was obtained during routine varicose vein surgery. The length was treated in five sections with different LEEDs (0 (control), 20, 40, 60, and 80 J/cm) with a 1920 nm EVL at 4W power, in a novel in vitro treatment model. The biological effects were assessed by histological staining of the samples for haematoxylin and eosin (HE) and Martius Scarlet Blue (MSB), and by immunofluorescent detection of p-p53 and VCAM-1.ResultsHistological analysis showed significant structural damage at LEEDs above 60 J/cm, especially in the intima and media, with the treatment at 80 J/cm causing perforation of the vein wall. In addition, there was a significant increase in p-p53 expression in treated tissue at 60 and 80 J/cm.ConclusionsUsing this ex vivo model, the results indicate that in vitro treatment with a 1920 nm EVL, at or above an LEED of 60 J/cm and 4 W power, causes significant vein wall cell death reaching deep into the media by a combination of direct thermal damage and apoptosis. A wavelength of 1920 nm appears to be effective for the endovenous ablation of truncal veins.

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“…It is widely accepted that sclerosants disrupt the cell membrane causing (i) endothelial cell (EC) death microscopically, and (ii) macroscopic vein wall damage, such as disruption of the subintima (i.e. the elastic tissue located underneath the endothelium) and mild alterations of the smooth muscle layer 24,25 .…”

Section: Introductionmentioning

confidence: 99%

In vitro and ex vivo evaluation of the biological performance of sclerosing foams

Bottaro

Paterson

Quercia

et al. 2019

Sci Rep

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Since the first reports on foam sclerotherapy, multiple studies have been conducted to determine the physical properties and behavior of foams, but relatively little is known about their biological effects on the endothelial cells lining the vessel wall. Moreover, a systematic comparison of the biological performance of foams produced with different methods has not been carried out yet. Herein, a 2D in vitro method was developed to compare efficacy of commercially available polidocanol injectable foam (PEM, Varithena) and physician-compounded foams (PCFs). Endothelial cell attachment upon treatment with foam was quantified as an indicator of therapeutic efficacy, and was correlated with foam physical characteristics and administration conditions. An ex vivo method was also developed to establish the disruption and permeabilisation of the endothelium caused by sclerosing agents. It relied on the quantitation of extravasated bovine serum albumin conjugated to Evans Blue, as an indicator of endothelial permeability. In our series of comparisons, PEM presented a greater overall efficacy compared to PCFs, across the different biological models, which was attributed to its drainage dynamics and gas formulation. This is consistent with earlier studies that indicated superior physical cohesiveness of PEM compared to PCFs.

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Media Damage Following Detergent Sclerotherapy Appears to be Secondary to the Induction of Inflammation and Apoptosis: An Immunohistochemical Study Elucidating Previous Histological Observations

Cited by 41 publications

References 24 publications

Detergent sclerosants at sub-lytic concentrations induce endothelial cell apoptosis through a caspase dependent pathway

Detergent sclerosants at sub-lytic concentrations induce endothelial cell apoptosis through a caspase dependent pathway

Histological and Immunofluorescent Analysis of a Large Tributary of the Great Saphenous Vein Treated with a 1920 nm Endovenous Laser: Preliminary Findings

In vitro and ex vivo evaluation of the biological performance of sclerosing foams

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