Expression of molecular mediators of apoptosis and their role in the pathogenesis of lower-extremity varicose veins

Ascher, Enrico; Jacob, Theresa; Hingorani, Anil; Tsemekhin, Boris; Gunduz, Yilmaz

doi:10.1067/mva.2001.113976

Cited by 51 publications

(66 citation statements)

References 20 publications

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“…Nevertheless, apoptosis was increased in endothelial cells and cells in the adventitia of varicose veins. Our fi ndings confi rm the limited occurrence of programmed cell death in varicose veins [20,21] .…”

Section: Discussionsupporting

confidence: 52%

Smooth Muscle Cell Hypertrophy in Varicose Veins Is Associated with Expression of Estrogen Receptor-β

Knaapen¹,

Somers²,

Bortier³

et al. 2005

J Vasc Res

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Varicose veins are characterized by dilated and thickened vein walls. This study examined whether the changes that occur in varicose veins are associated with smooth muscle cell (SMC) hypertrophy, cellular proliferation or apoptosis. Moreover, the association between SMC hypertrophy and the expression of the estrogen receptor-β (ERβ) was investigated. Varicose veins were obtained from male patients during vascular stripping surgery (n = 11) and nonvaricose veins during coronary bypass surgery, also from male subjects (n = 12). The cellular volume of the SMC in both the longitudinal and circular layer of the vessel wall was measured using stereological methods. Apoptosis was detected using the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling) technique. SMC proliferation and ERβ expression were investigated by immunohistochemistry. Neither in the longitudinal nor in the circular layer of the varicose vein wall were signs of apoptosis or proliferation present. However, the mean cellular volume of the SMC in the circular layer of the varicose veins was strongly increased (5,291 ± 363 µm³) as compared to non-varicose veins (2,812 ± 212 µm³, p < 0.001). Moreover, ERβ expression in the circular layer of varicose veins (63 ± 4%) significantly differed from nonvaricose veins (39 ± 4%; p = 0.001). Interestingly, the SMC volume correlated with ERβ expression (r = 0.71, p < 0.001). These data show that cell death or proliferation of SMC do not, or only rarely, occur in varicose veins. However, remodeling of varicose veins can mainly be attributed to increased volumes of the SMC of the circular layer and this increase correlates with ERβ expression.

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Section: Discussionsupporting

confidence: 52%

Smooth Muscle Cell Hypertrophy in Varicose Veins Is Associated with Expression of Estrogen Receptor-β

Knaapen¹,

Somers²,

Bortier³

et al. 2005

J Vasc Res

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“…Dysregulated apoptosis and cell cycle dysfunction occur in varicose veins 90 -94 . The overall number of apoptotic cells and activity are reduced in varicose compared with non-varicose veins 92,93,95 . Dedifferentiation of SMCs may be due to dysregulated apoptosis 96 .…”

Section: Smooth Muscle Cell Proliferation and Migrationmentioning

confidence: 99%

“…Bax is a member of the bcl-2 family and an inducer of apoptosis. PARP is an enzyme involved in genome surveillance and DNA repair, and is a macromolecular downstream substrate of apoptosis 93 . 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.…”

Section: Smooth Muscle Cell Proliferation and Migrationmentioning

confidence: 99%

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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“…Apoptosis of vascular cells was a prominent feature of blood vessel remodeling that occurs during normal development and many disorders of the vessel wall. It had been demonstrated that the overall number of apoptotic cells and activity were reduced in varicose compared with non-varicose veins (Bujan et al 2000;Ascher et al 2001). Ducasse et al provided evidence of decreased programmed cell death in the medial layer of human primary varicose veins (Ducasse et al 2008).…”

Section: Go Name Degree Apoptosis 10mentioning

confidence: 99%

MicroRNA Profiling in Great Saphenous Vein Tissues of Patients with Chronic Venous Insufficiency

Cui

Guang

Huang

et al. 2012

Tohoku J. Exp. Med.

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Chronic venous insufficiency (CVI) is a common disease characterized by structural and functional abnormalities of the venous system. Until recently, the pathogenesis of CVI remains largely unknown. MicroRNAs (miRNAs) are a family of endogenous small non-coding RNAs emerged as post-transcriptional gene repressors and play essential roles in diverse pathological processes including vascular disease. However, their roles in CVI have not been elucidated. In this study, we employed oligonucleotide microarrays to perform a genome-wide miRNAs profiling in the great saphenous vein (GSV) tissues of patients with CVI. Our results revealed a total of 14 miRNAs that are expressed differentially in GSV tissues. Among them nine miRNAs were found significantly up-regulated, while five miRNAs were downregulated significantly. Real-time RT-PCR verified statistically consistent expression of three selected miRNAs (miR-34a, miR-155 and miR-202) with microarrays analysis. These three miRNAs, which were described as crucial regulators in many biological processes and vascular diseases, might also play important roles in CVI. Functional annotation of target genes of differentially expressed miRNAs via bioinformatics approaches revealed that these predicted targets were significantly enriched and involved in several key signaling pathways important for CVI, including mitogen-activated protein kinase pathways, pathways in cancer, apoptosis, and cell cycle, and p53 signaling pathways. In summary, miRNAs might involve in multiple signaling pathways contributing to the pathological processes of CVI. These data may provide fundamental insights into the molecular basis of CVI, which may aid in designing novel approaches for prevention and treatment of this complex disease.Keywords: bioinformatics; chronic venous insufficiency; great saphenous vein; microarray; microRNA Tohoku J. Exp. Med., 2012 Dec, 228 (4), 341-350. © 2012 Tohoku University Medical Press Chronic venous insufficiency (CVI) is a complex medical condition characterized by structural and functional abnormalities of the venous system, which is commonly seen in humans. CVI is manifested with a range of signs, including varicose veins, trophic skin changes and venous ulcers. It has a considerable socioeconomic impact in many countries due to its high prevalence, cost of investigations and management, deterioration of the quality of life and loss of working days (Rabe and Pannier 2010). To date, in spite of numerous studies on CVI, the etiology and pathogenesis of CVI remains largely unknown.MicroRNAs (miRNAs) are a family of highly conserved, endogenous small non-coding RNAs (19-24nt) that post-transcriptionally repress gene expression via degradation or translational inhibition of their target mRNAs. They play important roles in nearly all physiological and pathological processes, including cell differentiation, proliferation, apoptosis, cardiovascular disease, and human cancers (Bartel 2004). There is mounting evidence suggesting that miRNAs had distinct expression profiles an...

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Expression of molecular mediators of apoptosis and their role in the pathogenesis of lower-extremity varicose veins

Cited by 51 publications

References 20 publications

Smooth Muscle Cell Hypertrophy in Varicose Veins Is Associated with Expression of Estrogen Receptor-β

Smooth Muscle Cell Hypertrophy in Varicose Veins Is Associated with Expression of Estrogen Receptor-β

Pathogenesis of primary varicose veins

MicroRNA Profiling in Great Saphenous Vein Tissues of Patients with Chronic Venous Insufficiency

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