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.

scholarly journals Dysregulations of MicroRNA and Gene Expression in Chronic Venous Disease

2020 ◽  
Vol 9 (5) ◽  
pp. 1251 ◽  
Author(s):  
Daniel P. Zalewski ◽  
Karol P. Ruszel ◽  
Andrzej Stępniewski ◽  
Dariusz Gałkowski ◽  
Jacek Bogucki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mononuclear Cells ◽  
Varicose Veins ◽  
Expression Profiles ◽  
Lower Limbs ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Operating Characteristics ◽  
Potential Biomarker ◽  
Pathologic Features

Chronic venous disease (CVD) is a vascular disease of lower limbs with high prevalence worldwide. Pathologic features include varicose veins, venous valves dysfunction and skin ulceration resulting from dysfunction of cell proliferation, apoptosis and angiogenesis. These processes are partly regulated by microRNA (miRNA)-dependent modulation of gene expression, pointing to miRNA as a potentially important target in diagnosis and therapy of CVD progression. The aim of the study was to analyze alterations of miRNA and gene expression in CVD, as well as to identify miRNA-mediated changes in gene expression and their potential link to CVD development. Using next generation sequencing, miRNA and gene expression profiles in peripheral blood mononuclear cells of subjects with CVD in relation to healthy controls were studied. Thirty-one miRNAs and 62 genes were recognized as potential biomarkers of CVD using DESeq2, Uninformative Variable Elimination by Partial Least Squares (UVE-PLS) and ROC (Receiver Operating Characteristics) methods. Regulatory interactions between potential biomarker miRNAs and genes were projected. Functional analysis of microRNA-regulated genes revealed terms closely related to cardiovascular diseases and risk factors. The study shed new light on miRNA-dependent regulatory mechanisms involved in the pathology of CVD. MicroRNAs and genes proposed as CVD biomarkers may be used to develop new diagnostic and therapeutic methods.

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.

scholarly journals Why Venous Leg Ulcers Have Difficulty Healing: Overview on Pathophysiology, Clinical Consequences, and Treatment

2020 ◽  
Vol 10 (1) ◽  
pp. 29
Author(s):  
Joseph D. Raffetto ◽  
Daniela Ligi ◽  
Rosanna Maniscalco ◽  
Raouf A. Khalil ◽  
Ferdinando Mannello
Keyword(s):  
Endothelial Cell ◽  
Reactive Oxygen ◽  
Compression Therapy ◽  
Venous Hypertension ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Leg Ulcers ◽  
Nitrogen Species ◽  
Venous Leg Ulcers ◽  
Tissue Metabolites

Venous leg ulcers (VLUs) are one of the most common ulcers of the lower extremity. VLU affects many individuals worldwide, could pose a significant socioeconomic burden to the healthcare system, and has major psychological and physical impacts on the affected individual. VLU often occurs in association with post-thrombotic syndrome, advanced chronic venous disease, varicose veins, and venous hypertension. Several demographic, genetic, and environmental factors could trigger chronic venous disease with venous dilation, incompetent valves, venous reflux, and venous hypertension. Endothelial cell injury and changes in the glycocalyx, venous shear-stress, and adhesion molecules could be initiating events in VLU. Increased endothelial cell permeability and leukocyte infiltration, and increases in inflammatory cytokines, matrix metalloproteinases (MMPs), reactive oxygen and nitrogen species, iron deposition, and tissue metabolites also contribute to the pathogenesis of VLU. Treatment of VLU includes compression therapy and endovenous ablation to occlude the axial reflux. Other interventional approaches such as subfascial endoscopic perforator surgery and iliac venous stent have shown mixed results. With good wound care and compression therapy, VLU usually heals within 6 months. VLU healing involves orchestrated processes including hemostasis, inflammation, proliferation, and remodeling and the contribution of different cells including leukocytes, platelets, fibroblasts, vascular smooth muscle cells, endothelial cells, and keratinocytes as well as the release of various biomolecules including transforming growth factor-β, cytokines, chemokines, MMPs, tissue inhibitors of MMPs (TIMPs), elastase, urokinase plasminogen activator, fibrin, collagen, and albumin. Alterations in any of these physiological wound closure processes could delay VLU healing. Also, these histological and soluble biomarkers can be used for VLU diagnosis and assessment of its progression, responsiveness to healing, and prognosis. If not treated adequately, VLU could progress to non-healed or granulating VLU, causing physical immobility, reduced quality of life, cellulitis, severe infections, osteomyelitis, and neoplastic transformation. Recalcitrant VLU shows prolonged healing time with advanced age, obesity, nutritional deficiencies, colder temperature, preexisting venous disease, deep venous thrombosis, and larger wound area. VLU also has a high, 50–70% recurrence rate, likely due to noncompliance with compression therapy, failure of surgical procedures, incorrect ulcer diagnosis, progression of venous disease, and poorly understood pathophysiology. Understanding the molecular pathways underlying VLU has led to new lines of therapy with significant promise including biologics such as bilayer living skin construct, fibroblast derivatives, and extracellular matrices and non-biologic products such as poly-N-acetyl glucosamine, human placental membranes amnion/chorion allografts, ACT1 peptide inhibitor of connexin 43, sulodexide, growth factors, silver dressings, MMP inhibitors, and modulators of reactive oxygen and nitrogen species, the immune response and tissue metabolites. Preventive measures including compression therapy and venotonics could also reduce the risk of progression to chronic venous insufficiency and VLU in susceptible individuals.

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.

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.

Epidemiology and Genetics of Venous Thromboembolism and Chronic Venous Disease

2021 ◽  
Vol 128 (12) ◽  
pp. 1988-2002
Author(s):  
Richard A. Baylis ◽  
Nicholas L. Smith ◽  
Derek Klarin ◽  
Eri Fukaya
Keyword(s):  
Venous Thromboembolism ◽  
Association Studies ◽  
Venous Hypertension ◽  
Chronic Venous Disease ◽  
Future Research ◽  
Venous Disease ◽  
Genome Wide Association Studies ◽  
Mortality And Morbidity ◽  
Genome Wide ◽  
Venous Thromboembolic

Venous disease is a term that broadly covers both venous thromboembolic disease and chronic venous disease. The basic pathophysiology of venous thromboembolism and chronic venous disease differ as venous thromboembolism results from an imbalance of hemostasis and thrombosis while chronic venous disease occurs in the setting of tissue damage because of prolonged venous hypertension. Both diseases are common and account for significant mortality and morbidity, respectively, and collectively make up a large health care burden. Despite both diseases having well-characterized environmental components, it has been known for decades that family history is an important risk factor, implicating a genetic element to a patient’s risk. Our understanding of the pathogenesis of these diseases has greatly benefited from an expansion of population genetic studies from pioneering familial studies to large genome-wide association studies; we now have multiple risk loci for each venous disease. In this review, we will highlight the current state of knowledge on the epidemiology and genetics of venous thromboembolism and chronic venous disease and directions for future research.

Chronic venous insufficiency and post-thrombotic syndrome

ESC CardioMed ◽  
2018 ◽  
pp. 2817-2822
Author(s):  
Robert T. Eberhardt ◽  
Joseph D. Raffetto
Keyword(s):  
Chronic Venous Insufficiency ◽  
Venous Insufficiency ◽  
Surgical Techniques ◽  
Duplex Ultrasound ◽  
Venous Hypertension ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Severity Of Disease ◽  
Venous Valves ◽  
Venous Function

Chronic venous disease is a common problem with a significant impact upon both afflicted individuals and the healthcare system. Normal venous function requires patency of the axial veins with a series of venous valves, and muscle pumps. Dysfunction of any of the normal structures may lead to venous hypertension and development of chronic venous insufficiency. There is a spectrum of manifestations of chronic venous insufficiency including skin changes and venous leg ulcers. Venous duplex ultrasound may be used to confirm the diagnosis and provide anatomical detail. The treatment of chronic venous insufficiency will be based on the severity of disease and guided by anatomical and pathophysiological considerations. Compressive garments have been a mainstay in treatment. Interventional methods have replaced many traditional surgical techniques but are still typically reserved for unsatisfactory response to conservative measures.

scholarly journals Pressure dynamics in chronic venous disease

2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Taimur Saleem ◽  
Seshadri Raju
Keyword(s):  
Ex Vivo ◽  
Venous Pressure ◽  
Venous Hypertension ◽  
Chronic Venous Disease ◽  
Abdominal Pressure ◽  
Venous Disease ◽  
Venous Obstruction ◽  
Resting Pressure ◽  
Air Plethysmography ◽  
Focal Stenosis

Peripheral venous pressure is regulated by central and peripheral mechanisms. Peripheral venous hypertension is an important pathologic component of chronic venous disease and is present in about two-third of patients with chronic venous disease. It can result from reflux, obstructive lesions or high arterial inflow. The dominant influence in patients with peripheral venous hypertension appears to be obstruction rather than reflux. Reflux can be superficial or deep or both. In about 70% of patients with reflux, valvular incompetence is present in the superficial, deep and perforator systems in some combination. In an ex vivo experimental model, conduit pressure increased with smaller native or functional caliber, focal stenosis and increased post-capillary inflow. Venous pressure in the lower limb can be measured in a variety of ways: supine resting pressure, erect resting pressure and ambulatory venous pressure. These measurements are affected by factors such as intra-abdominal pressure, intra-thoracic pressure, gravity, venoarteriolar reflux, valve reflux and venous obstruction. Venous obstruction is associated with elevated supine pressures while reflux is associated with elevated erect resting and ambulatory venous pressures. Ambulatory venous pressure reflects venous hypertension in patients with advanced venous disease. However, our investigation has shown that ambulatory venous pressure hypertension is rarely present if air plethysmography testing is negative. Consideration maybe given to the omission of the ambulatory venous pressure testing if air plethysmography testing is normal.

Altered elastase—alpha1-antitrypsin balance in the blood of patients with chronic venous disease

2015 ◽  
Vol 31 (2) ◽  
pp. 125-132 ◽  
Author(s):  
M Budzyn-Napierala ◽  
M Iskra ◽  
Z Krasinski ◽  
W Turkiewicz ◽  
B Gryszczynska ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Early Stage ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Leukocyte Elastase ◽  
Vein Wall ◽  
Alpha1 Antitrypsin ◽  
Antitrypsin Activity ◽  
Wall Injury

Objectives Although leukocyte elastase is suspected to be involved in the damage of vein wall during chronic venous disease, the equilibrium between this protease and its inhibitor, alpha1-antitrypsin, has not yet been evaluated. The aim of the present study was to determine the relationship between leukocyte elastase and alpha1-antitrypsin, in the blood of patients with chronic venous disease. Patients and methods The concentration and the activity of leukocyte elastase along with the activity of alpha1-antitrypsin were evaluated in the blood of 55 chronic venous disease patients. The results were compared with those obtained in 33 healthy age and sex-matched volunteers. Results A significant decrease in the leukocyte elastase activity that correlated with an increased alpha1-antitrypsin activity was observed in the serum of patients with mild clinical symptoms of chronic venous disease. Conclusions The results of the study did not confirm a hypothesis about an important role of proteolytic activity of leukocyte elastase in the vein wall injury mechanism. They show that the leukocyte elastase–alpha1-antitrypsin balance is rather shifted toward antiprotease activity, especially in an early stage of chronic venous disease.

scholarly journals Identification of Transcriptomic Differences between Lower Extremities Arterial Disease, Abdominal Aortic Aneurysm and Chronic Venous Disease in Peripheral Blood Mononuclear Cells Specimens

2021 ◽  
Vol 22 (6) ◽  
pp. 3200
Author(s):  
Daniel P. Zalewski ◽  
Karol P. Ruszel ◽  
Andrzej Stępniewski ◽  
Dariusz Gałkowski ◽  
Jacek Bogucki ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Peripheral Blood Mononuclear Cells ◽  
Mononuclear Cells ◽  
Arterial Disease ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Peripheral Blood Mononuclear ◽  
Abdominal Aortic ◽  
Blood Mononuclear Cells

Several human tissues are investigated in studies of molecular biomarkers associated with diseases development. Special attention is focused on the blood and its components due to combining abundant information about systemic responses to pathological processes as well as high accessibility. In the current study, transcriptome profiles of peripheral blood mononuclear cells (PBMCs) were used to compare differentially expressed genes between patients with lower extremities arterial disease (LEAD), abdominal aortic aneurysm (AAA) and chronic venous disease (CVD). Gene expression patterns were generated using the Ion S5XL next-generation sequencing platform and were analyzed using DESeq2 and UVE-PLS methods implemented in R programming software. In direct pairwise analysis, 21, 58 and 10 differentially expressed genes were selected from the comparison of LEAD vs. AAA, LEAD vs. CVD and AAA vs. CVD patient groups, respectively. Relationships between expression of dysregulated genes and age, body mass index, creatinine levels, hypertension and medication were identified using Spearman rank correlation test and two-sided Mann–Whitney U test. The functional analysis, performed using DAVID website tool, provides potential implications of selected genes in pathological processes underlying diseases studied. Presented research provides new insight into differences of pathogenesis in LEAD, AAA and CVD, and selected genes could be considered as potential candidates for biomarkers useful in diagnosis and differentiation of studied diseases.

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