Pathogenesis of primary chronic venous disease: Insights from animal models of venous hypertension

Bergan, John J.; Pascarella, Luigi; Schmid‐Schönbein, Geert W.

doi:10.1016/j.jvs.2007.09.028

Cited by 110 publications

(95 citation statements)

References 78 publications

(75 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The assessment of ECM remodeling in varicose veins in humans provides information at an established level of the disease, whereas animal models of varicose vein development do not precisely reflect human disease pathogenesis [42]. Nevertheless, according to the results of our study, we can conclude that varicose vein development does not influence TGF-β1 mRNA levels in vein walls and is further accompanied by a decrease in total TGF-β1 levels and expression of its active/latent forms.…”

Section: Discussionmentioning

confidence: 47%

Influence of thrombophlebitis on TGF-Î˛1 and its signaling pathway in the vein wall.

Kowalewski

Małkowski²,

Gacko³

et al. 2011

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

Extensive extracellular matrix remodeling of the vein wall is involved in varicose veins pathogenesis. This process is controlled by numerous factors, including peptide growth factors. The aim of the study was to evaluate influence of thrombophlebitis on TGF-β1 and its signaling pathway in the vein wall. TGF-β1 mRNA levels, growth factor content and its expression were evaluated by RT-PCR, ELISA, and western blot methods, respectively, in the walls of normal veins, varicose veins and varicose veins complicated by thrombophlebitis. Western blot analysis was used to assess TGF-β receptor type II (TGF-β RII) and p-Smad2/3 protein expression in the investigated material. Unchanged mRNA levels of TGF-β1, decreased TGF-β1 content, as well as decreased expression of latent and active forms of TGF-β1 were found in varicose veins. Increased expression of TGF-β RII and p-Smad2/3 were found in varicose veins. Thrombophlebitis led to increased protein expression of the TGF-β1 active form and p-Smad2/3 in the vein wall compared to varicose veins. TGF-β1 may play a role in the disease pathogenesis because of increased expression and activation of its receptor in the wall of varicose veins. Thrombophlebitis accelerates activation of TGF-β1 and activity of its receptor in the varicose vein wall.

show abstract

Section: Discussionmentioning

confidence: 47%

Influence of thrombophlebitis on TGF-Î˛1 and its signaling pathway in the vein wall.

Kowalewski

Małkowski²,

Gacko³

et al. 2011

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

show abstract

“…pregnancy, and family history have been identified (Ruckley et al 2002;Carpentier et al 2004), the molecular mechanisms underlying the pathogenesis of this disease remains vague. Various theories, such as the hemodynamic alteration causing venous hypertension (Bergan et al 2008), the incompetence of the saphenous venous valves (Duran et al 2000), the leukocyte-trapping hypothesis (Korthuis and Unthank 2000) and the weak vein wall hypothesis (Meissner et al 2007) had been put forward to explain the pathogenesis of varicose veins and CVI. However, these theories might remain some uncertainties and had been conflicting with each other.…”

Section: Discussionmentioning

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.

View full text Add to dashboard Cite

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...

show abstract

“…Changes in hemodynamic forces impacting the vein wall such as shear stress may induce inflammation, and subsequently the remodeling of venous walls and valves, contributing to varicose veins and other venous pathologies (Pascarella et al, 2005). A specific example that links altered shear stress, the endothelium, and venous disease is a study performed by Bergan et al (2008). The study involved a surgical alteration to produce venous hypertension and altered shear stress, which led to an inflammatory reaction in the vein wall driven by endothelial activation and neutrophil infiltration, resulting in thrombus formation.…”

Section: Flow Effects On Pathologymentioning

confidence: 99%

Impedance analysis of endothelial cells undergoing orbital shear stress.

Gruenthal¹

View full text Add to dashboard Cite

Understanding the endothelium at the cellular level could further knowledge of the cardiovascular system as a whole and could therefore lead to advances in the prevention and treatment of cardiovascular disease. Electric cell-substrate impedance sensing is an in vitro technique that can be used for observing the behavior of endothelial cells in real-time using a fluid flow environment to simulate the circulatory system. This study examined the effect of fluid shear stress on human umbilical vein endothelial cells using electrochemical impedance spectroscopy (impedance sensing). Circuit models were fit to empirical data to measure cell layer resistance and capacitance changes, and to determine if data trends follow those of previously published findings. Information derived from transendothelial electrical resistance measurements, about changes in cell layer permeability when subjected to varying shear stress conditions within an orbiting circular well, was used to draw conclusions aided by microscopic images of the cells.

show abstract

Pathogenesis of primary chronic venous disease: Insights from animal models of venous hypertension

Cited by 110 publications

References 78 publications

Influence of thrombophlebitis on TGF-Î˛1 and its signaling pathway in the vein wall.

Influence of thrombophlebitis on TGF-Î˛1 and its signaling pathway in the vein wall.

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

Impedance analysis of endothelial cells undergoing orbital shear stress.

Contact Info

Product

Resources

About