Dysregulated Apoptosis in Primary Varicose Veins

Ducasse, Éric; Giannakakis, K.; Chevalier, Julie; Dasnoy, D.; Puppinck, P; Speziale, Francesco; Fiorani, P; Faraggiana, Tullio

doi:10.1016/j.ejvs.2004.12.012

Cited by 33 publications

(30 citation statements)

References 50 publications

(58 reference statements)

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“…It has been demonstrated immunohistochemically that the expression of bax and caspase 9 is significantly reduced in SMCs from varicose compared with non-varicose veins. The expression of caspase 8 and Fas in SMCs, however, does not differ significantly between varicose and non-varicose veins 90,91 . Therefore, the intrinsic rather than the extrinsic pathway seems dysregulated in varicose veins as bax and caspase 9 are involved in the former, whereas caspase 8 and Fas are involved in the latter 90,91 (Fig.…”

Section: Smooth Muscle Cell Proliferation and Migrationmentioning

confidence: 80%

“…hypoxia, mechanical stretch and low shear stress) Endothelial injury and leucocyte activation (inflammation) 90 . Improperly regulated apoptosis may contribute to pathological conditions involving faulty DNA repair mechanisms and cell cycle disruption.…”

Section: Smooth Muscle Cell Proliferation and Migrationmentioning

confidence: 99%

“…Improperly regulated apoptosis may contribute to pathological conditions involving faulty DNA repair mechanisms and cell cycle disruption. Such conditions include cancer, Alzheimer's disease, ischaemic heart disease and spinal muscular atrophy 90 . Dysregulated apoptosis and cell cycle dysfunction occur in varicose veins 90 -94 .…”

Section: Smooth Muscle Cell Proliferation and Migrationmentioning

confidence: 99%

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Pathogenesis of primary varicose veins

Lim

Davies

2009

British Journal of Surgery

238

206

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Positive family history, age, sex and pregnancy are important risk factors for varicose vein formation. Areas of intimal hyperplasia and smooth muscle cell proliferation are often noted in varicose veins, although regions of atrophy are also present. The total elastin content in varicose as opposed to non-varicose veins is reduced; changes in overall collagen content are uncertain. Matrix metalloproteinases (MMPs), including MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9, and tissue inhibitor of metalloproteinase (TIMP) 1 and TIMP-3 are upregulated in varicose veins. Activation of the endothelium stimulates the recruitment of leucocytes and the release of growth factors, leading to smooth muscle cell proliferation and migration. Dysregulated apoptosis has also been demonstrated in varicose veins. An understanding of the pathophysiology of varicose veins is important in the identification of potential therapeutic targets and treatment strategies.

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Section: Smooth Muscle Cell Proliferation and Migrationmentioning

confidence: 80%

Section: Smooth Muscle Cell Proliferation and Migrationmentioning

confidence: 99%

Section: Smooth Muscle Cell Proliferation and Migrationmentioning

confidence: 99%

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Pathogenesis of primary varicose veins

Lim

Davies

2009

British Journal of Surgery

238

206

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“…A previous study has demonstrated that MGP regulated apoptosis at different stages of cell differentiation [57]. Decreased apoptosis in the medial layer of varicose veins has been described [59, 60]. Involvement of MGP in the decreased programmed varicose cell death will require further investigation.…”

Section: Discussionmentioning

confidence: 98%

Identification of Differentially Expressed Genes in Human Varicose Veins: Involvement of Matrix Gla Protein in Extracellular Matrix Remodeling

et al. 2007

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This study was designed to identify the global pattern of differentially expressed genes in human varicose veins. Using suppressive subtractive hybridization, we identified overexpression of genes known to be associated with extracellular matrix remodeling, including collagen III, tissue inhibitor of metalloproteinases I, dermatopontin, matrix Gla protein (MGP) and tenascin C. Real-time polymerase chain reaction analysis confirmed the differential expression of these genes. The overexpression of MGP transcript was associated with increased MGP level in varicose veins, in particular the undercarboxylated form of the protein. Smooth muscle cells from varicose veins showed increased proliferation rate and enhanced matrix mineralization. This observation correlated with the presence of ectopic mineralization areas in the varicose vein walls. The use of warfarin, to inhibit MGP activity, or siRNA targeting MGP transcript induced a reduction in the exacerbated proliferation of varicose vein smooth muscle cells. Our results suggest that high expression of MGP in varicose veins may contribute to venous wall remodeling by affecting proliferation and mineralization processes probably through impaired carboxylation of MGP. In addition, suppressive subtractive hybridization results also produce a profile of differentially expressed genes in varicose veins, in particular extracellular matrix components. Further study of these genes will provide insights into their specific roles in the etiology of venous disease.

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“…In addition, they presented healthy increase of collagen fibers and decrease in density and size of elastic fibers. The immunoreactivity to caspase-9 and Bax in muscular layer cells was significantly smaller in varicose veins when compared to healthy ones, demonstrating a low apoptotic regulation [11]. Beside these concepts about chronic varicose veins, one well carried out study showed that two-minute distensions of 300mmHg in intact human saphenous veins induced p38 activation, which is associated with apoptosis [6].…”

Section: -Representative Photomicrographs Of Immunohistochemical Analmentioning

confidence: 99%

Expression of apoptosis in human saphenous vein grafts in restoration of blood flow through coronary bypass surgery

Tirapelli

Tirapelli²,

Dalio³

et al. 2009

Rev Bras Cir Cardiovasc

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Expressão da apoptose em enxertos de veias safenas humana para restauração do fluxo sanguíneo coronariano por derivaçãoExpression of apoptosis in human saphenous vein grafts in restoration of blood flow through coronary bypass surgery Methods: Fresh isolated grafts of human saphenous vein were assigned as control or distended (D) for fifteen seconds at 100, 200 and 300 mmHg. The degree of apoptotic caspases 3, 8, 9 and anti-apoptotic protein Bcl-2 expression were assessed by immunohistochemistry.Results: Fresh isolated segments of distended human saphenous veins presented similar apoptotic protein expression when compared with control veins. However, the Bcl-2 expression was significantly higher in the 300 mmHg distended segments compared with the control vein.Conclusion: These findings show that intact segments of human saphenous veins submitted to distensions at different pressures have similar apoptotic proteins expression when compared with non-distended control veins. Therefore, brief distensions commonly performed during surgical harvesting do not trigger apoptosis, and probably are not involved on the physiopathological mechanisms that lead to graft failure. Descriptors: Apoptosis. Cardiac surgical procedures. Saphenous vein.Correspondence address: R. Manoel Ache, 921/91 -Jardim Irajá. Ribeirão

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Dysregulated Apoptosis in Primary Varicose Veins

Abstract: Apoptosis is down regulated in the medial layer of varicose veins. This dysregulation of the cellular mechanism that maintains normal tissue integrity is mediated through the intrinsic apoptotic pathway and may be among the causes of primary varicose veins.

Cited by 33 publications

References 50 publications

Pathogenesis of primary varicose veins

Pathogenesis of primary varicose veins

Identification of Differentially Expressed Genes in Human Varicose Veins: Involvement of Matrix Gla Protein in Extracellular Matrix Remodeling

Expression of apoptosis in human saphenous vein grafts in restoration of blood flow through coronary bypass surgery

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