Chronic Venous Disease and the Leukocyte-Endothelium Interaction: From Symptoms to Ulceration

Angiology ◽  
2005 ◽  
Vol 56 (6_suppl) ◽  
pp. S11-S19 ◽  
Author(s):  
A. N. Nicolaides
Keyword(s):  
Inflammatory Process ◽  
Varicose Veins ◽  
Signs And Symptoms ◽  
Venous Hypertension ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Vein Wall ◽  
Venous Flow ◽  
Inflammatory Cascade ◽  
The Many

The mechanisms regulating varicose vein development and the subsequent skin sequelae seen in chronic venous disease (CVD) have been investigated recently. Despite the diversity of signs and symptoms associated with the disease, it seems likely that they are related to venous hypertension. Valvular incompetence is the most important cause of venous hypertension. Recent findings suggest that inflammatory processes are involved in the structural remodeling in venous valves and in the vein wall, leading to valvular incompetence and the development of varicose veins. This has been shown by Ono and colleagues, who found infiltration of valve leaflets and the venous wall by leukocytes (monocytes and tissue macrophages) in all valve specimens from patients with CVD and in none from controls. Further work by Takase and colleagues confirmed this hypothesis. Vein wall remodeling is likely to involve the complex interplay of a range of factors, including an altered ratio between metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), and elevated levels of cytokines and growth factors favor an alteration of the extracellular matrix. Neutrophils and mast cells and their interaction with the venous endothelium are believed to play an important role in the initiation of the inflammatory response in CVD. The transmission of high venous pressures to the dermal microcirculation results in the stimulation of an inflammatory process in which cytokine and growth factor release leads to leukocyte migration into the interstitium and the initiation of further inflammatory events. This process is associated with the intense dermal fibrosis and tissue remodeling seen in chronic venous insufficiency. The many manifestations of the disease are frequently associated with symptoms usually ascribed to CVD. The proportion of patients with symptoms increases with increasing CEAP clinical classes, but the mechanisms underlying symptom appearance have not been elucidated. It has been postulated that it is related to the inflammatory cascade of events seen at all stages of CVD and in which the leukocyte and its interaction with the endothelium play a key role. It is increasingly believed that the emerging twin themes of disturbed venous flow patterns and chronic inflammation underlie and link all the manifestations of the disease. Among the many pathophysiologic mechanisms at work, the leukocyte-endothelium interactions seem to be important in many aspects of the disease and have been identified as a possible target for pharmacologic intervention. Pharmacologic agents that could attenuate various elements of the inflammatory cascade and inhibit the inflammatory process might offer a greater opportunity to prevent future morbidity. It seems reasonable to speculate that such treatment could reduce the risk of CVD progression if applied as soon as the first symptoms appear.

Endovenous management of varicose veins

2004 ◽  
Vol 19 (4) ◽  
pp. 163-169 ◽  
Author(s):  
S Soumian ◽  
A H Davies
Keyword(s):  
Varicose Veins ◽  
Signs And Symptoms ◽  
Venous Hypertension ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Foam Sclerotherapy ◽  
High Prevalence ◽  
Promising Treatment ◽  
Developed World

Objective: Chronic venous disease has made a considerable socio-economical impact in the developed world due to its high prevalence and cost of management. Venous hypertension gives rise to significant signs and symptoms that are indications for treatment. Though the mainstay of treatment currently is surgery, it may not be the ideal choice in some cases considering the heterogeneous spectrum of venous disease. Recent alternative endovenous treatments have shown a lot of promise in successfully treating this condition. The aim of this review was to assess the long-term effectiveness of these treatments. Methods: A Medline-based review of literature was carried out. Results: Foam sclerotherapy seems to be a very promising treatment for venous disease, as short-term results have shown good results in terms of outcomes, low morbidity and cost. New endovenous techniques such as radiofrequency and laser ablation are attractive considering the absence of groin scar and subsequent neovascularization, as well as very little bruising and discomfort. Conclusions: There is no clear evidence yet regarding the long-term effectiveness of these relatively new endovenous techniques.

scholarly journals Understanding Chronic Venous Disease: A Critical Overview of Its Pathophysiology and Medical Management

2021 ◽  
Vol 10 (15) ◽  
pp. 3239
Author(s):  
Miguel A. Ortega ◽  
Oscar Fraile-Martínez ◽  
Cielo García-Montero ◽  
Miguel A. Álvarez-Mon ◽  
Chen Chaowen ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Current Knowledge ◽  
Varicose Veins ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Significant Loss ◽  
Venous Hypertension ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Environmental Agents

Chronic venous disease (CVD) is a multifactorial condition affecting an important percentage of the global population. It ranges from mild clinical signs, such as telangiectasias or reticular veins, to severe manifestations, such as venous ulcerations. However, varicose veins (VVs) are the most common manifestation of CVD. The explicit mechanisms of the disease are not well-understood. It seems that genetics and a plethora of environmental agents play an important role in the development and progression of CVD. The exposure to these factors leads to altered hemodynamics of the venous system, described as ambulatory venous hypertension, therefore promoting microcirculatory changes, inflammatory responses, hypoxia, venous wall remodeling, and epigenetic variations, even with important systemic implications. Thus, a proper clinical management of patients with CVD is essential to prevent potential harms of the disease, which also entails a significant loss of the quality of life in these individuals. Hence, the aim of the present review is to collect the current knowledge of CVD, including its epidemiology, etiology, and risk factors, but emphasizing the pathophysiology and medical care of these patients, including clinical manifestations, diagnosis, and treatments. Furthermore, future directions will also be covered in this work in order to provide potential fields to explore in the context of CVD.

Endocrine mechanisms in the pathogenesis of primary varicosis

Phlebologie ◽  
2013 ◽  
Vol 42 (01) ◽  
pp. 13-18 ◽  
Author(s):  
S. Schnabl ◽  
A. Strölin ◽  
Ch. Busch
Keyword(s):  
Chronic Venous Insufficiency ◽  
Regulatory Networks ◽  
Venous Insufficiency ◽  
Varicose Veins ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Extensive Literature ◽  
Vein Wall ◽  
Extensive Literature Search ◽  
Relaxin 2

SummaryIntroduction: Varicose veins affect up to 40 % of men and up to 51 % of women. The patho-physiology of primary varicosis (chronic venous insufficiency, CVI) is poorly understood. Here, the available data on possible endocrine mechanisms in healthy and varicose veins are reviewed.Methods: An extensive literature search was conducted in PubMed using the following key words: Chronic venous insufficiency, CVI, chronic venous disease, CVD, varicosis, saphenous vein, pathogenesis, hormone.Results: Several theories ranging from incompetence of the valves to functional, biological or morphologic changes in different layers of the vein wall have been proposed. However, an increasing body of evidence suggests that endocrine mechanisms might be involved in the pathogenesis of primary varicosis. In this respect a growing number of hormones (e.g. estrogen, progesterone, relaxin-2, and oxytocin) and their receptors have been linked to primary varicosis in experimental, pharmacological and histological studies.Conclusion: In summary, endocrine-based mechanisms seem to play a role in the pathogenesis of primary varicosis. This opens up the perspective for pharmacological treatments targeting the various described endocrine regulatory networks.

Critical Buckling Pressure of Veins

2008 ◽  
Author(s):  
Ricky Martinez ◽  
Cesar A. Fierro ◽  
Hai-Chao Han
Keyword(s):  
Critical Pressure ◽  
Varicose Veins ◽  
Axial Strain ◽  
Venous Pressure ◽  
Underlying Mechanism ◽  
Venous Hypertension ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Jugular Veins ◽  
Critical Buckling Pressure

Vein tortuosity is often seen as a consequence of venous hypertension and chronic venous disease. However, the underlying mechanism of vein tortuosity is unclear. The aim of this study was to test the hypothesis that hypertensive pressure causes vein buckling that leads to tortuous veins. We determined the buckling pressure of porcine jugular veins and tested the mechanical properties of these veins. Our results demonstrated that veins buckle when the transmural pressure exceeds a critical pressure that is not much higher than normal venous pressure. The critical pressure was found to be strongly related to the axial strain in the veins. Our results are useful in understanding the development of varicose veins.

Predicted burden of venous disease

2016 ◽  
Vol 31 (1_suppl) ◽  
pp. 74-79 ◽  
Author(s):  
Sarah Onida ◽  
Alun Huw Davies
Keyword(s):  
Varicose Veins ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Venous Ulceration ◽  
Increased Risk ◽  
Future Burden ◽  
Clinical Signs And Symptoms

Chronic venous disease is a common condition with clinical signs and symptoms ranging from spider veins, to varicose veins, to active venous ulceration. Both superficial and deep venous dysfunction may be implicated in the development of this disease. Socio-economic factors are shaping our population, with increasing age and body mass index resulting in significant pressure on healthcare systems worldwide. These risk factors also lead to an increased risk of developing superficial and/or deep venous insufficiency, increasing disease prevalence and morbidity. In this chapter, the authors review the current and future burden of chronic venous disease from an epidemiological, quality of life and economic perspective.

Endovenous laser ablation is an effective treatment for great saphenous vein incompetence in teenagers

2015 ◽  
Vol 31 (3) ◽  
pp. 198-202
Author(s):  
Piotr Terlecki ◽  
Stanislaw Przywara ◽  
Marek Iłżecki ◽  
Karol Terlecki ◽  
Piotr Kawecki ◽  
...  
Keyword(s):  
Laser Ablation ◽  
Saphenous Vein ◽  
Great Saphenous Vein ◽  
Current Knowledge ◽  
Varicose Veins ◽  
Signs And Symptoms ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Invasive Treatment ◽  
Endovenous Laser Ablation

Objectives The current knowledge of chronic venous disease in teenagers and its treatment is very limited. The aim of the study is to present our experience and the available literature data on the treatment of varicose veins in teenagers with endovenous laser ablation of the great saphenous vein. Methods Five patients, aged 15–17 years, were qualified for surgery, based on typical signs and symptoms of chronic venous disease. Minimally invasive treatment with endovenous laser ablation of the great saphenous vein was applied. Results The technical success of surgery was achieved in all patients. Over a 2-year follow-up we did not observe any case of recanalisation of the great saphenous vein, recurrence of varicose veins, or serious complications, such as deep vein thrombosis or pulmonary embolism. One patient presented with resolving of post-operative bruising, and two cases of local numbness were transient. Conclusions Endovenous laser ablation of the great saphenous vein in the treatment of chronic venous disease in teenagers is effective and safe. The method provides excellent cosmetic effects, very short recovery time and high levels of patient satisfaction.

scholarly journals Chronic venous disease patients show increased IRS-4 expression in the great saphenous vein wall

2021 ◽  
Vol 49 (9) ◽  
pp. 030006052110412
Author(s):  
Miguel A Ortega ◽  
Oscar Fraile-Martínez ◽  
Cielo García-Montero ◽  
Fernando Ruiz-Grande ◽  
Silve Barrena ◽  
...  
Keyword(s):  
Varicose Veins ◽  
Adaptor Protein ◽  
Chronic Venous Disease ◽  
Histopathological Study ◽  
Venous Disease ◽  
Vein Wall ◽  
Functional Changes ◽  
Molecular Alterations ◽  
High Prevalence ◽  
Mitogen Activated Protein

Objectives Chronic venous disease (CVeD) is a multifactorial and debilitating condition that has a high prevalence in Western countries and an important associated socioeconomic burden. Varicose veins (VVs) are the most common manifestations of CVeD. Pathologically, many morphological and functional changes have been described in VVs, which most notably affect venous wall integrity. Previous studies have found several molecular alterations that negatively affect normal cell signaling pathways. Insulin receptor substrate (IRS)-4 is a central adaptor protein that is closely related to insulin/insulin-like growth factor-1 signaling upstream, phosphatidylinositol 3-kinase/Akt or mitogen-activated protein kinases downstream, and other proteins. These molecular pathways have been implicated in CVeD pathogenesis. Thus, the aim of our study was to identify the role of IRS-4 in VV tissue. Methods We conducted a histopathological study to analyze IRS-4 protein expression in CVeD patients compared with healthy controls. Results Our results demonstrate a significant increase in IRS-4 expression in VV tissue. Conclusions IRS-4 may be implicated in CVeD development and progression. Therefore, IRS-4 could be a potential diagnostic or therapeutic target for patients with this condition.

scholarly journals Generation of reactive oxygen species by a sufficient, insufficient and varicose vein wall.

2011 ◽  
Vol 58 (1) ◽  
Author(s):  
Wirginia Krzyściak ◽  
Mariusz Kózka
Keyword(s):  
Reactive Oxygen Species ◽  
Free Radicals ◽  
Varicose Veins ◽  
Reactive Oxygen ◽  
Chronic Venous Disease ◽  
Clinical State ◽  
Venous Disease ◽  
Oxygen Species ◽  
Vein Wall ◽  
Venous Diseases

Despite numerous theories, the etiology and pathogenesis of primary varicose veins remain unclear. The etiology of chronic venous diseases (CVDs) known as chronic venous insufficiency (CVI) is related to leukocyte trapping. Leukocyte trapping involves trapping of white cells in vessel walls followed by their activation and translocation outside the vessel. Release of reactive oxygen species (ROS) from trapped white cells has been documented. Superoxide dismutase (SOD) directly inhibits the generation of free radicals and compounds that are produced during oxidation by ROS, such as malonyldialdehyde (MDA). The aim of this study was to determine the involvement of free radicals in the etiology of venous changes. The following material was used for the study: fragments of sufficient or insufficient venous system and varices from 31 patients diagnosed with chronic venous disease in the 2nd or 3rd degree, according to clinical state, etiology, anatomy and pathophysiology (CEAP), which were qualified for surgical procedure. The levels of oxidative stress markers strongly correlated with lesions observed by USG in insufficient and varicose veins. In both a higher concentration of MDA was observed, which is a sign of lipid peroxidation. Antioxidative mechanisms, SOD activity and total antioxidative power expressed as FRAP were inversely proportional to MDA concentration. In insufficient and varicose veins both FRAP and SOD activities were significantly lower than in normal veins. The severity of clinical changes was inversely dependent on the efficiency of scavenging of ROS, which additionally proves the participation of free radicals in pathogenesis of CVDs.

Genetic polymorphisms of vein wall remodeling in chronic venous disease: a narrative and systematic review

Blood ◽  
2014 ◽  
Vol 124 (8) ◽  
pp. 1242-1250 ◽  
Author(s):  
Vighnesh Bharath ◽  
Susan R. Kahn ◽  
Alejandro Lazo-Langner
Keyword(s):  
Systematic Review ◽  
Varicose Veins ◽  
Chronic Venous Disease ◽  
Current Evidence ◽  
Postthrombotic Syndrome ◽  
Venous Disease ◽  
Genetic Associations ◽  
Vein Wall ◽  
Venous Ulceration ◽  
Therapeutic Implications

Abstract Chronic venous disease encompasses a spectrum of disorders caused by an abnormal venous system. They include chronic venous insufficiency, varicose veins, lipodermatosclerosis, postthrombotic syndrome, and venous ulceration. Some evidence suggests a genetic predisposition to chronic venous disease from gene polymorphisms associated mainly with vein wall remodeling. The literature exploring these polymorphisms has not been reviewed and compiled thus far. In this narrative and systematic review, we present the current evidence available on the role of polymorphisms in genes involved in vein wall remodeling and other pathways as contributors to chronic venous disease. We searched the EMBASE, Medline, and PubMed databases from inception to 2013 for basic science or clinical studies relating to genetic associations in chronic venous disease and obtained 38 relevant studies for this review. Important candidate genes/proteins include the matrix metalloproteinases (extracellular matrix degradation), vascular endothelial growth factors (angiogenesis and vessel wall integrity), FOXC2 (vascular development), hemochromatosis (involved in venous ulceration and iron absorption), and various types of collagen (contributors to vein wall strength). The data on associations between these genes/proteins and the postthrombotic syndrome are limited and additional studies are required. These associations might have future prognostic and therapeutic implications.

Duffy antigen / receptor for chemokines correlates with inflammatory reaction in rats with venous hypertension: implication for the pathogenesis of primary chronic venous disease

VASA ◽  
2014 ◽  
Vol 43 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Weibin Huang ◽  
Weiwei Qin ◽  
Lei Lv ◽  
Haoyv Deng ◽  
Hao Zhang ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Early Stage ◽  
Antigen Receptor ◽  
Venous Hypertension ◽  
Skin Tissue ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Dependent Manner ◽  
Time Points ◽  
Duffy Antigen

Background: Duffy antigen / receptor for chemokines (DARC) possesses high affinity for several chemokine subgroups of CC and CXC. Although DARC has been shown to play a role in many inflammatory diseases, its effect on chronic venous disease (CVD) remains unidentified. We explored whether the expression of DARC in skin tissue was activated under venous hypertension as well as the relationships between DARC and inflammation. Materials and methods: The inflammation in a rat model of venous hypertension caused by a femoral arterial-venous fistula (AVF) was studied. At specified intervals the pressure in the femoral veins was recorded within 42 days. Hindlimb skin specimens were harvested at different time points. The expressions of DARC, interleukin-8 (IL-8), and monocyte chemotactic protein-1 (MCP-1) in skin tissue were examined. Mononuclear cells infiltrated in skin tissue were detected. Results: Femoral venous pressures in AVF groups increased significantly at different time points (P < 0.01). DARC was expressed in skin tissue and its expression level increased significantly in AVF groups from the 7nd day on and was enhanced in a time-dependent manner within 42 days (P < 0.05). Meanwhile, both MCP-1 and IL-8 had higher levels, accompanied by increased mononuclear cells infiltrating into skin tissue (P < 0.05). Conclusions: A rat AVF model which can maintain venous hypertension for at least 42 days is competent for researching the pathogenesis of CVD. DARC, which plays a role in the inflammation of skin tissue under venous hypertension, may become a new molecular target for diagnosis and treatment of CVD at a very early stage.

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