Varicose Veins Show Enhanced Chemokine Expression

Solá, L. Del Río; Aceves, Mónica; Dueñas, Antonio; González-Fajardo, J.A.; Vaquero, Carlos; Crespo, Mariano Sánchez; García-Rodríguez, Carmen

doi:10.1016/j.ejvs.2009.07.021

Cited by 38 publications

(25 citation statements)

References 31 publications

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“…Moreover, biological functions of PPP3R1 suggest its involvement in VVs etiology (Table 2). In particular, it induces MCP-1 production, which was shown to be enhanced in VVs 55 , 56 . Finally, a recent study demonstrated that expression of PPP3R1 is increased in the venous tissue of VVs patients compared with veins of healthy individuals (fold change = 1.5) 57 .…”

Section: Resultsmentioning

confidence: 91%

Varicose veins of lower extremities: insights from the first large-scale genetic study

Shadrina

Sharapov

Shashkova

et al. 2018

Preprint

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27Varicose veins of lower extremities (VVs) are a common multifactorial vascular disease. 28Genetic factors underlying VVs development remain largely unknown. Here we report the first 29 large-scale study of VVs performed on a freely available genetic data of 408,455 European-30 ancestry individuals. We identified 7 reliably associated loci that explain 10% of the SNP-based 31 heritability, and prioritized the most likely causal genes CASZ1, PPP3R1, EBF1, STIM2, and 32 HFE. Genetic correlation analysis confirmed known epidemiological associations and found 33 genetic overlap with various traits including fluid intelligence score, educational attainment, 34 smoking, and pain. Finally, we observed causal effects of height, weight, both fat and fat-free 35 mass, and plasma levels of MICB and CD209 proteins. 36All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/368365 doi: bioRxiv preprint first posted online Jul. 13, 2018; 3 Varicose veins (VVs) are one of the clinical manifestations of chronic venous disease 37 posing both a cosmetic and medical problem. VVs can be found in different parts of the body, 38 but most commonly occur in the lower extremities. Prevalence estimates of this condition vary 39 across ethnic groups ranging from 2-4% in the Northern group of the Cook Islands to 50-60% in 40 some countries of the Western world 1 The cumulative evidence from epidemiological, family, and genetic association studies 52 strongly indicates that there is a hereditary component in VVs etiology [6][7][8] . However, despite 53 progress in this field [9][10][11][12] , current knowledge of the genetic basis of this pathology is far from 54 being complete. Elucidating genes involved in susceptibility to VVs would help to identify key 55 molecular players in the disease initiation, provide deeper insights into its pathogenesis, and 56 eventually contribute to development of improved targeted therapy aimed at VVs treating and 57 preventing. 58Large-scale biobanks linked to electronic health records open up unparalleled opportunities 59 to investigate the genetics of complex traits. Today, UK Biobank is the largest repository that 60 contains information on genotypes and phenotypes for half a million participating individuals 13 . 61This resource is open to all bona fide researchers, and access to data is provided upon approval 62All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/368365 doi: bioRxiv preprint first posted online Jul. 13, 2018; 4 of their application and payment of necessary costs. However, the need to incur high costs 63 related to data access and computation can be an insurmountable obstacle for those...

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Section: Resultsmentioning

confidence: 91%

Varicose veins of lower extremities: insights from the first large-scale genetic study

Shadrina

Sharapov

Shashkova

et al. 2018

Preprint

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“…The effect of disturbed flow on vascular endothelium has been deeply evaluated in vitro in models of standard endothelium [11, 22–24] and, more recently, in an ex vivo model of primary venous endothelial cells (VEC) isolated from surgical saphenous specimens of CVI patients [12, 14]. Moreover, higher expression of proinflammatory cytokines/chemokines has been demonstrated at RNA level in varicose veins compared to control veins [13]. In further studies performed in the pathologic VEC model, we suggested the link between hemodynamic forces and the proinflammatory status of CVI, documented by a correlation between key hemodynamic parameters and the ex vivo endothelial release of cytokines/chemokines, underlining in particular the possible contribution of soluble mediators such as PDGF-BB and osteoprotegerin [14, 25], a key regulator of the two TNF family members RANKL and TRAIL [26, 27].…”

Section: Discussionmentioning

confidence: 99%

“…This hypothesis is furthermore supported by the evidence that, even though we have demonstrated that the systemic profile matched the local profile, these three molecules showed the major levels at the varicose vein site. Of note, since RANTES acts as chemotactic molecule for leukocytes [13, 31], it actually appears to represent one of the hubs in the cytokine network (Figure 4(a)) and a link between the endothelial disease and the inflammatory process.…”

Section: Discussionmentioning

confidence: 99%

“…It is still unclear what initiates the inflammatory process in the vein wall, but it has been shown that the persistent venous hypertension characterizing CVI leads to an inflammatory response primarily mediated by leukocytes and involving cascades of cytokines/chemokines, matrix metalloproteinases activation, and alteration of endothelial cellular functions [8–11]. Expression of pro-inflammatory cytokines and chemokines has been reported in patients with varicose veins confirming the role of inflammation in CVI [12, 13]. In a recent work, we have shown a correlation between the PDGF-BB released by patient-derived vein endothelial cell (VEC) cultures and relevant hemodynamic parameters measured in vivo into the venous segments from which the VEC was isolated upon surgical ablation [14].…”

Section: Introductionmentioning

confidence: 99%

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Modulation of Circulating Cytokine-Chemokine Profile in Patients Affected by Chronic Venous Insufficiency Undergoing Surgical Hemodynamic Correction

Tisato

Zauli

Gianesini

et al. 2014

Journal of Immunology Research

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The expression of proinflammatory cytokines/chemokines has been reported in in vitro/ex vivo settings of chronic venous insufficiency (CVI), but the identification of circulating mediators that might be associated with altered hemodynamic forces or might represent innovative biomarkers is still missing. In this study, the circulating levels of 31 cytokines/chemokines involved in inflammatory/angiogenic processes were analysed in (i) CVI patients at baseline before surgical hemody namic correction, (ii) healthy subjects, and (iii) CVI patients after surgery. In a subgroup of CVI patients, in whom the baseline levels of cytokines/chemokines were analyzed in paired blood samples obtained from varicose vein and forearm vein, EGF, PDGF, and RANTES were increased at the varicose vein site as compared to the general circulation. Moreover, while at baseline, CVI patients showed increased levels of 14 cytokines/chemokines as compared to healthy subjects, 6 months after surgery, 11 cytokines/chemokines levels were significantly reduced in the treated CVI patients as compared to the CVI patients before surgery. Of note, a patient who exhibited recurrence of the disease 6 months after surgery, showed higher levels of EGF, PDGF, and RANTES compared to nonrecurrent patients, highlighting the potential role of the EGF/PDGF/RANTES triad as sensitive biomarkers in the context of CVI.

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“…This study found a marked expression of monocyte-chemoattractant protein (MCP)-1, macrophage-inflammatory protein (MIP)-1 α , MIP-1 β , interferon- γ -inducible protein (IP)-10, interleukin (IL)-8, and RANTES in varicose veins, suggesting that chemokines might play an important role in their pathophysiology by recruiting leucocytes to the vein wall and contributing to inflammation and edema. It is known that MCP-1, MIP-1 α , MIP-1 β , and IP-10 are chemoattractants for monocytes/macrophages, IL-8 is able to attract neutrophils, and RANTES is a chemotactic molecule for leucocytes [101]. Taken together, there is ample evidence of a role of inflammation in varicose vein formation and that inflammation is produced at least in part by venous hypertension.…”

Section: Stretch Signaling Pathways In Varicose Veinsmentioning

confidence: 99%

Varicose Veins: Role of Mechanotransduction of Venous Hypertension

Atta

2012

International Journal of Vascular Medicine

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Varicose veins affect approximately one-third of the adult population and result in significant psychological, physical, and financial burden. Nevertheless, the molecular pathogenesis of varicose vein formation remains unidentified. Venous hypertension exerted on veins of the lower extremity is considered the principal factor in varicose vein formation. The role of mechanotransduction of the high venous pressure in the pathogenesis of varicose vein formation has not been adequately investigated despite a good progress in understanding the mechanomolecular mechanisms involved in transduction of high blood pressure in the arterial wall. Understanding the nature of the mechanical forces, the mechanosensors and mechanotransducers in the vein wall, and the downstream signaling pathways will provide new molecular targets for the prevention and treatment of varicose veins. This paper summarized the current understanding of mechano-molecular pathways involved in transduction of hemodynamic forces induced by blood pressure and tries to relate this information to setting of venous hypertension in varicose veins.

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Varicose Veins Show Enhanced Chemokine Expression

Abstract: Varicose veins showed increased expression of several chemokines compared to control veins. A non-significant reduction of activation was observed following treatment with ASA for 15 days.

Cited by 38 publications

References 31 publications

Varicose veins of lower extremities: insights from the first large-scale genetic study

Varicose veins of lower extremities: insights from the first large-scale genetic study

Modulation of Circulating Cytokine-Chemokine Profile in Patients Affected by Chronic Venous Insufficiency Undergoing Surgical Hemodynamic Correction

Varicose Veins: Role of Mechanotransduction of Venous Hypertension

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