Evaluation of apoptosis in varicose vein disease complicated by superficial vein thrombosis

Filis, Konstantinos; Kavantzas, Nikolaos; Dalainas, Ilias; Galyfos, George; Karanikola, Evridiki; Toutouzas, Konstantinos; Tsioufis, Constantinos; Sigala, Fragiska

doi:10.1024/0301-1526/a000360

Cited by 8 publications

(5 citation statements)

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“…Ducasse et al 28 have also documented that the process of programmed cell death is inhibited in varicose veins and suggested that the parietal cells in varicose veins live longer and become dysfunctional, which may lead to weakening or dilatation of the venous wall. Others have shown increased vein wall apoptosis in thrombophlebitic saphenous and varicose veins, and associated increased vein wall apoptosis with venous hypertension, 32,47 which are opposed to the results of the current study. We think that the differences in results involve disease severity, diseased category, and the part of vein taken etc.…”

Section: Discussioncontrasting

confidence: 99%

Dysregulated apoptosis of the venous wall in chronic venous disease and portal hypertension

Wang

et al. 2016

Phlebology

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Introduction The etiology of varicose veins remains elusive. We hypothesized that abnormal cell cycle events in the vein wall may contribute to changes in the structural integrity, thus predisposing to the development of varicosities. The present study was designed to determine whether or not the same molecular apoptotic pathway exists between great saphenous and splenic veins. Methods Thirty-six samples of diseased splenic veins and varicose great saphenous veins were collected. Twenty-five samples of control splenic and great saphenous veins were also collected. The apoptotic cell proteins expression was immunohistochemically stained with antibodies (anti-Bax and anti-Bcl-xl). Apoptosis was evaluated by the terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay and immunofluorescence staining. The morphology of apoptotic cells was observed with an electron microscope. Results The apoptotic ratio in walls (intima and media) of diseased splenic vein and varicose great saphenous vein groups were significantly lower than the corresponding regions in the splenic vein and great saphenous vein groups ( p < 0.01), respectively. A significant difference was not noted in the ratio change of apoptotic cells between the diseased splenic vein and varicose great saphenous vein groups ( p > 0.05). The high positive expression of Bcl-xl proteins was detected in the diseased splenic vein and varicose great saphenous vein groups, respectively. While the high positive expression of Bax proteins was also observed in the splenic vein and great saphenous vein groups, respectively. Electron microscopic observations confirmed that endothelial and smooth muscle cells in diseased splenic vein, varicose great saphenous vein, splenic vein, and great saphenous vein walls exhibited apoptotic morphologic features, such as fuzzy mitochondrial cristae, medullary changes, and margination of the nuclear chromatin. Conclusions Our results showed the same dysregulation of apoptosis via the intrinsic pathway in diseased splenic veins and varicose great saphenous veins. This observational study suggests that apoptotic down-regulation in the veins wall is a cause of diseased splenic veins and varicose great saphenous veins, but does not exclude the possibility that other mechanisms are involved.

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Section: Discussioncontrasting

confidence: 99%

Dysregulated apoptosis of the venous wall in chronic venous disease and portal hypertension

Wang

et al. 2016

Phlebology

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“…59 Moreover, a histological study in human superficial vein segments found higher apoptosis activities in those containing thrombus. 60 The diverse pathways involved in cellular senescence converge on p53, a transcription factor controlling cell cycle, growth arrest, and apoptosis. 10,61 However, very little is known regarding p53 and the risk of thrombosis.…”

Section: Discussionmentioning

confidence: 99%

The endothelial tumor suppressor p53 is essential for venous thrombus formation in aged mice

Bochenek

Bauer

Gogiraju³

et al. 2018

Blood Advances

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Key Points• Deletion of p53 in endothelial cells prevents venous thrombosis in aged, but not in adult, mice.• Neutralization of heparanase in aged mice using TFPI2 peptides restores the thrombotic phenotype of adult mice. End.p53-KO mice were protected from vein thrombosis. Analysis of primary endothelial cells from aged mice or human vein endothelial cells after induction of replicative senescence revealed significantly increased early growth response gene-1 (Egr1) and heparanase expression, and plasma factor Xa levels were elevated in aged End.p53-WT, but not in End.p53-KO mice. Increased endothelial Egr1 and heparanase expression also was observed after doxorubicin-induced p53 overexpression, whereas p53 inhibition using pifithrin-a reduced tissue factor (TF) expression. Importantly, inhibition of heparanase activity using TF pathway inhibitor-2 (TFPI2) peptides prevented the enhanced venous thrombus formation in aged mice and restored it to the thrombotic phenotype of adult mice.Our findings suggest that p53 accumulation and heparanase overexpression in senescent endothelial cells are critically involved in mediating the increased risk of venous thrombosis with age and that heparanase antagonization may be explored as strategy to ameliorate the prothrombotic endothelial phenotype with age.

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“…Others have shown increased vein wall apoptosis in thrombophlebitic saphenous veins and varicose veins and associate it with venous hypertension. 13,14 However, our work state is the opposite. We think that the differences in results involve diseased severity and the part of vein taken etc.…”

Section: Discussionmentioning

confidence: 70%

“…12 (morphological, ultrastructural, cell proliferation and TUNEL method analysis were performed), and Filis et al. 13,14 (the expression of Bax, p53, caspase 3, Bcl-2, Bcl-6, Bcl-xs, Bcl-xl and Ki-67 were detected), while Ascher et al. 9,15 (apoptosis was detected by TUNEL assay; expression of bcl-2 and cyclin D1 was noted by standard immunohistochemical techniques) concluded that down-regulation of apoptosis occurred in primary varicose veins.…”

Section: Introductionmentioning

confidence: 99%

Assessment of apoptotic cells in the wall of thrombophlebitic saphenous vein

Han

Wang

et al. 2015

Phlebology

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Evaluation of apoptosis in varicose vein disease complicated by superficial vein thrombosis

Abstract: The vein wall in SVT shows increased pro-apoptotic activity compared to uncomplicated disease and normal veins. Whether increased vein wall cell apoptosis is a causative factor for SVT in varicose veins disease or a repairing mechanism of the thrombosis itself needs further research.

Cited by 8 publications

References 0 publications

Dysregulated apoptosis of the venous wall in chronic venous disease and portal hypertension

Dysregulated apoptosis of the venous wall in chronic venous disease and portal hypertension

The endothelial tumor suppressor p53 is essential for venous thrombus formation in aged mice

Assessment of apoptotic cells in the wall of thrombophlebitic saphenous vein

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