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

Abstract

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.

Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen species

“…Then, apoptosomes activate caspase 9 and initiate the chain reaction of caspase cascade. These processes are defined as caspase dependent-apoptosis50. On the other hand, AIF and Endo G are released from perforated mitochondria, translocated into the nucleus and induce chromosomal DNA fragmentations.…”

Comparison of tetradecyl sulfate versus polidocanol injections for stabilisation of joints that regularly dislocate in an Ehlers-Danlos population

“…Note: Side effects from sclerosants at doses used in varicose veins and arteries (30–150 mg/dose) include: hypersensitivity, arterial and venous thrombosis, cardiac arrhythmias, visual/neurological disturbances and skin ulcerations 23. Differences in strength have known differences in effects 24–26. We have occasionally seen a rash, but we have not seen the rest of these side effects at this clinic with the low-dose (1.1–2.5 mg) treatments.…”

Telangiectatic Matting is Associated with Hypersensitivity and a Bleeding Tendency

“…In a number of recent in vitro studies, this group has demonstrated that detergent sclerosants induce endothelial activation, apoptosis and release of inflammatory and angiogenic cytokines at low concentrations. 20,21 Treating the telangiectasias without treating the underlying veins may result in inflammation and subsequent angiogenesis and formation of TM. This can follow sclerotherapy, endovenous laser therapy, and even venous surgery.…”