Effect of TGF-beta1 on MMP/TIMP and TGF-beta1 receptors in great saphenous veins and its significance on chronic venous insufficiency

2016 ◽  
Vol 32 (5) ◽  
pp. 334-341 ◽  
Author(s):  
Pedro Serralheiro ◽  
Elisa Cairrão ◽  
Cláudio J Maia ◽  
Marina João ◽  
Carlos M Costa Almeida ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Venous Insufficiency ◽  
Venous Insufficiency ◽  
Transforming Growth Factor ◽  
Varicose Veins ◽  
Bypass Graft ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Wall Structure ◽  
Vein Wall ◽  
Tgf Β1

Objectives Transforming growth factor-beta1 (TGF-β1) may participate in local chronic inflammatory processes in varicose veins and in venous wall structure modifications through regulation of matrix metalloproteinases (MMP) and their inhibitors (tissue inhibitor of metalloproteinase (TIMP)). The aim of this study was to analyze the effect of TGF-β1 in the vein wall, namely on the gene expression of selected MMP, TIMP and TGF-β1 receptors. Methods Healthy vein samples were harvested from eight subjects who underwent coronary bypass graft surgery with great saphenous vein. Each vein sample was divided into two segments, which were cultivated separately in vitro (one of the segments had TGF-β1 added) and then submitted to gene expression analysis. Results In the TGF-β1 supplemented group, there was a general increase in the mean gene expression. Specifically, expression of MMP9, MMP12, TIMP1 and TIMP2 were statistically significant. Conclusion The results of this study demonstrate that the gene expression of MMP9, MMP12, TIMP1 and TIMP2 was influenced by the addition of TGF-β1. These results may be translated to chronic venous insufficiency framework and suggest involvement of TGF-β1 in the vein wall pathology.

scholarly journals Chronic venous insufficiency after COVID-19: management of edema and pain syndromes

2021 ◽  
Vol 18 (2) ◽  
pp. 151-153
Author(s):  
F. Kh. Nizamov
Keyword(s):  
Chronic Diseases ◽  
Chronic Venous Insufficiency ◽  
Venous Insufficiency ◽  
Clinical Symptoms ◽  
Varicose Veins ◽  
Clinical Manifestations ◽  
Pain Syndrome ◽  
Venous Stasis ◽  
Vein Wall ◽  
Vas Scores

Introduction. COVID-19 infection raises many questions regarding the health condition of patients after they have had COVID-19. The aim of this study is to examine the characteristic symptoms of chronic venous insufficiency in the postcovid period.Materials and methods. The materials that were used for work included the results of studying the medical aid appealability, characteristic symptoms, diagnosis and treatment of symptoms of chronic venous insufficiency in persons who have had the coronavirus infection. 47 patients presented with complaints about deterioration of their condition after they had had COVID-19 over March to September 2021 period. Methods: general clinical examiniation, ultrasound angioscanning of veins of the lower extremities, laboratory coagulation tests.Results and discussion. Before deterioration, calf circumference was measured 22–24 cm at a typical measurement site in most patients (89%), after covid infection it reached 26–27 cm. Varicose veins remained soft, without intravascular formations, edema was often bilateral, asymmetric, pain was described as constant (5–6 VAS scores), patients had prominent signs of lymphostasis. 35 out of 47 people received diosmin-based venotonic drug of Russian manufacture at a dose of 1000 mg/day (one tablet twice a day), the course of treatment lasted one to two months. After that period, the edema subsided in 85% of patients, the severity of pain syndrome significantly reduced (up to 2–3 VAS scores). With regard to chronic venous insufficiency in patients with chronic diseases of lower extremity veins (mostly varicose and post-thrombotic diseases), the significant progress of disease was observed in almost 94% of follow-up cases. Diosmin is the main drug that is prescribed to treat chronic venous insufficiency. The drug has an angioprotective and venotonic effect, reduces the vein wall elasticity, increases venous tone, and decreases venous stasis, reduces capillary permeability and fragility, and increases their resistance, improves microcirculation and lymphatic drainage.Сonclusions. In the postcovid period, clinical symptoms of some chronic diseases occur/worsen, including clinical manifestations of chronic venous insufficiency. The use of Russian diosmin-based drug for the management of edema and pain syndrome is very promising.

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.

scholarly journals EVALUATION OF THE MINIMAL EFFECTIVE FOAM SCLEROSANT CONCENTRATION AT SCLEROTHERAPY OF VARICOSE VEINS IN THE LOWER EXTREMITIES

2019 ◽  
Vol 111 (3) ◽  
pp. 11-20
Author(s):  
Khrystyna Korolova
Keyword(s):  
Side Effects ◽  
Chronic Venous Insufficiency ◽  
Venous Insufficiency ◽  
Histopathological Examination ◽  
Varicose Veins ◽  
Post Treatment ◽  
Vein Wall ◽  
Negative Side ◽  
Chemical Agents ◽  
Negative Side Effects

Chronic venous insufficiency is a widespread, global problem and continuously progresses with increasing age. Actual is a question of treatment of various classes of chronic venous insufficiency. Today, due to the widespread introduction of instrumental techniques and chemical agents, the era of minimally invasive interventions that compete with classical venectomies has begun. The gold standard for treating the initial manifestations of chronic venous insufficiency is sclerotherapy. It has been used to treat varicose veins since the beginning of the last century. In chemical sclerotherapy, various chemical agents are used, which, first of all, contribute to damage, dehydration and destruction of endothelial cells, which leads to the elimination of veins. All sclerosants are a compromise between efficacy and toxicity. In the scientific world, discussions are still ongoing and there is insufficient clinical data regarding the optimal choice of sclerosant and its concentration. The aim of this study was to study the histopathological changes in the vein wall, which can be caused by different concentrations of foam sclerosants, and to study the main negative side effects that occur in patients treated with these concentrations of sclerosants. Our study included 40 patients who were hospitalized from December 2017 to May 2019 with major varicose veins in combination with reticular varicose veins or telangiectasias (C2 - C4a class of varicose veins according to CEAP classification), patients underwent open venectomy followed by repeated sclerotherapy in distant period. Patients were randomized into 3 main groups of 10 people who were injected with the most common concentrations of polidocanol: 0.5%, 1% and 3%. The comparison group was 10 people with a similar pathology. Polidocanol was injected in foam form the day before surgery - venectomy. During venectomy, previously marked segments of the veins were carefully removed and sent for histopathological examination. general assessment was carried out according to a system that reflected the degree of damage to the vein wall in points. Three weeks after venectomy, all patients underwent sclerotherapy of small veins using sclerosants of the same concentration as before surgery. Clinical evaluation of post-treatment negative events was performed twice: on the second day and in a month. The results of the study confirm that changes in the vascular wall are already caused when using 0.5% foam polidocanol. The most pronounced and profound changes are caused by the action of 3% foam polidocanol, which is accompanied by a large number of negative side effects in the post-treatment period. The most optimal for sclerotherapy of veins with a diameter of 5-7 mm is 1% concentration. When this concentration is injected, there is enough damage to the vein for its further obliteration, which is not accompanied by as many negative manifestations as a higher concentration. The results of the study may be useful for phlebologists who use sclerotherapy to treat the initial manifestations of chronic venous insufficiency.

Features of postoperative period in patients with chronic venous insufficiency: phlebectomy versus thermal ablation

2020 ◽  
pp. 64-75
Author(s):  
E. Burleva ◽  
O. Smirnov ◽  
S. Tyurin
Keyword(s):  
Postoperative Period ◽  
Chronic Venous Insufficiency ◽  
Thermal Ablation ◽  
Venous Insufficiency ◽  
Clinical Symptoms ◽  
Varicose Veins ◽  
Statistical Processing ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

The purpose of the study was to conduct a comparative assessment of the course of the postoperative period after phlebectomy and thermal ablation in patients with varicose veins of the lower extremities in the system of the great saphenous vein (GSV) with class C2 of chronic venous insufficiency (CVI) — CEAP class C2. Materials and methods: 455 patients (455 limbs) with CEAP class C2. Group 1 (n = 154) received stripping + minimally invasive phlebectomy; Group 2 — endovenous laser ablation (EVLA) of GSV trunk + sclerotherapy of varicose veins; 3 group (n = 150) — radiofrequency ablation (RFA) of the GSV + sclerotherapy. All patients were united by a single tactical solution — the elimination of pathological vertical reflux in GSV. In each group, patients were with similar hemodynamic profile were selected (Group 1 = 63; Group 2 = 61; Group 3 = 61). The course of the postoperative period (from 2 days to 2 months) was compared for pain (visual analog scale — VAS), clinical symptoms of chronic venous insufficiency, degree of satisfaction (Darvall questionnaire), and duration of disability. Statistical processing was carried out using Excel programs for Windows XP, MedCalc® (version 11.4.2.0., Mariakerke, Belgium). Results: Postoperative pain is more pronounced (during day 1 for Group 1–4.0, Group 2–3.0, Group 3–2.0) and more prolonged (up to 4 days) after open surgeries (p < 0.05). The dynamics of the clinical symptoms of CVI (including varicose syndrome and use of compression therapy) could not be fully evaluated in connection with the ongoing sclerotherapy procedures for patients of Groups 2 and 3. Satisfaction of patients with aesthetic aspects was higher than expected in all groups. Reliable statistical differences proved decrease in days of disability (Group 1–14; Group 2–4; Group 3–3) and earlier return to physical activities and work in patients after thermal ablation in comparison with phlebectomy. Conclusion: The study shows that all three methods for eliminating vertical reflux in the GSV can be proposed for a large category of patients with CEAP of class C3 and C2. Medical and social rehabilitation of patients using endovascular thermal ablation technologies proceeds faster, which is beneficial both for the patients and for society.

scholarly journals Complex fibroblast response to glucocorticoids may underlie variability of clinical efficacy in the vocal folds

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ryosuke Nakamura ◽  
Shigeyuki Mukudai ◽  
Renjie Bing ◽  
Michael J. Garabedian ◽  
Ryan C. Branski
Keyword(s):  
Gene Expression ◽  
Transforming Growth Factor ◽  
Regulation Of Gene Expression ◽  
Vocal Folds ◽  
Global Changes ◽  
Rna Seq ◽  
Fibrotic Response ◽  
Group A ◽  
Tgf Β1 ◽  
Nuclear Receptor Subfamily

AbstractSimilar to the hypertrophic scar and keloids, the efficacy of glucorticoids (GC) for vocal fold injury is highly variable. We previously reported dexamethasone enhanced the pro-fibrotic effects of transforming growth factor (TGF)-β as a potential mechanism for inconsistent clinical outcomes. In the current study, we sought to determine the mechanism(s) whereby GCs influence the fibrotic response and mechanisms underlying these effects with an emphasis on TGF-β and nuclear receptor subfamily 4 group A member 1 (NR4A1) signaling. Human VF fibroblasts (HVOX) were treated with three commonly-employed GCs+ /-TGF-β1. Phosphorylation of the glucocorticoid receptor (GR:NR3C1) and activation of NR4A1 was analyzed by western blotting. Genes involved in the fibrotic response, including ACTA2, TGFBR1, and TGFBR2 were analyzed by qPCR. RNA-seq was performed to identify global changes in gene expression induced by dexamethasone. GCs enhanced phosphorylation of GR at Ser211 and TGF-β-induced ACTA2 expression. Dexamethasone upregulated TGFBR1, and TGFBR2 in the presence of TGF-β1 and increased active NR4A1. RNA-seq results confirmed numerous pathways, including TGF-β signaling, affected by dexamethasone. Synergistic pro-fibrotic effects of TGF-β were observed across GCs and appeared to be mediated, at least partially, via upregulation of TGF-β receptors. Dexamethasone exhibited diverse regulation of gene expression including NR4A1 upregulation consistent with the anti-fibrotic potential of GCs.

scholarly journals Periadventitial Delivery of Simvastatin‐Loaded Microparticles Attenuate Venous Neointimal Hyperplasia Associated With Arteriovenous Fistula

2020 ◽  
Vol 9 (24) ◽  
Author(s):  
Chenglei Zhao ◽  
Sean T. Zuckerman ◽  
Chuanqi Cai ◽  
Sreenivasulu Kilari ◽  
Avishek Singh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Arteriovenous Fistula ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Neointimal Hyperplasia ◽  
Systemic Delivery ◽  
Tgf Β1

Background Venous neointimal hyperplasia and venous stenosis (VS) formation can result in a decrease in arteriovenous fistula (AVF) patency in patients with end‐stage renal disease. There are limited therapies that prevent VNH/VS. Systemic delivery of simvastatin has been shown to reduce VNH/VS but local delivery may help decrease the side effects associated with statin use. We determined if microparticles (MP) composed of cyclodextrins loaded with simvastatin (MP‐SV) could reduce VS/VNH using a murine arteriovenous fistula model with chronic kidney disease. Methods and Results Male C57BL/6J mice underwent nephrectomy to induce chronic kidney disease. Four weeks later, an arteriovenous fistula was placed and animals were randomized to 3 groups: 20 μL of PBS or 20 μL of PBS with 16.6 mg/mL of either MP or MP‐SV. Animals were euthanized 3 days later and the outflow veins were harvested for quantitative reverse transcriptase–polymerase chain reaction analysis and 28 days later for immunohistochemistical staining with morphometric analysis. Doppler ultrasound was performed weekly. Gene expression of vascular endothelial growth factor‐A ( Vegf‐A ), matrix metalloproteinase‐9 ( Mmp‐9 ), transforming growth factor beta 1 ( Tgf‐β1 ), and monocyte chemoattractant protein‐1 ( Mcp‐1 ) were significantly decreased in MP‐SV treated vessels compared with controls. There was a significant decrease in the neointimal area, cell proliferation, inflammation, and fibrosis, with an increase in apoptosis and peak velocity in MP‐SV treated outflow veins. MP‐SV treated fibroblasts when exposed to hypoxic injury had decreased gene expression of Vegf‐A and Mmp‐9 . Conclusions In experimental arteriovenous fistulas, periadventitial delivery of MP‐SV decreased gene expression of Vegf‐A , Mmp‐9 , Tgf‐β1 and Mcp‐1, VNH/VS, inflammation, and fibrosis.

Pathogenesis of varicose veins and cellular pathophysiology of chronic venous insufficiency

2017 ◽  
pp. 61-72
Author(s):  
Deoranie N. Abdel-Naby ◽  
Walter N. Duran ◽  
Brajesh K. Lal ◽  
Frank T. Padberg Jr. ◽  
Peter J. Pappas
Keyword(s):  
Chronic Venous Insufficiency ◽  
Venous Insufficiency ◽  
Varicose Veins

scholarly journals Effect and mechanism of vitamin D activation disorder on liver fibrosis in biliary atresia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Song Sun ◽  
Menghua Xu ◽  
Peijun Zhuang ◽  
Gong Chen ◽  
Kuiran Dong ◽  
...  
Keyword(s):  
Vitamin D ◽  
Liver Fibrosis ◽  
Biliary Atresia ◽  
Transforming Growth Factor ◽  
Serum Vitamin ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Control Group ◽  
Serum Vitamin D ◽  
Duct Ligation ◽  
Tgf Β1

AbstractTo investigate the mechanism of 25 hydroxyvitamin D (25(OH)D) deficiency in children with biliary atresia (BA) and its effect on liver fibrosis. The serum vitamin D and 25(OH)D, and expression of 25 hydroxylase (CYP2R1 and CYP27A1) in the liver of BA patients were detected and compared with those in the control group. We investigated the effect of differential expression of CYP2R1 in hepatocytes on the expression of genes related to liver fibrosis in primary hepatic stellate cells (HSCs) of BA and animal models of cholestasis. The ratio of 25(OH)D/vitamin D in the BA group was significantly lower than that in the control group. The mRNA and protein expression of CYP2R1 and CYP27A1 in liver tissue of the BA group was significantly lower than that in the control group. Exogenous active vitamin D (calcitriol) inhibited the proliferation and migration of primary HSCs isolated from BA patients, and reduced the expression of fibrosis-related genes in vitro. Downregulation of expression of CYP2R1 in hepatocytes increased expression of transforming growth factor (TGF)-β1, collagen (Col)-1α1 and tissue inhibitor of metalloproteinase (TIMP)-1, and decreased the expression of matrix metalloproteinase (MMP)-2 in cocultured primary HSCs of BA. Upregulation of expression of CYP2R1 in mice with bile duct ligation significantly increased the level of 25(OH)D, decreased the expression of TGF-β1, Col-1α1 and TIMP-1, and increased the expression of MMP-2. Children with BA have impaired vitamin D activation due to CYP2R1 deficiency. The dysactivation of vitamin D can promote the proliferation and activation of HSCs and participate in the development of hepatic fibrosis in BA.

scholarly journals Klippel–Trénaunay Syndrome – A Very Rare and Interesting Syndrome

2015 ◽  
Vol 9 ◽  
pp. CCRPM.S21645 ◽  
Author(s):  
Deepak Sharma ◽  
Sachin Lamba ◽  
Aakash Pandita ◽  
Sweta Shastri
Keyword(s):  
Soft Tissue ◽  
Vascular Malformation ◽  
Chronic Venous Insufficiency ◽  
Venous Insufficiency ◽  
Varicose Veins ◽  
Lower Limbs ◽  
Port Wine ◽  
Bone Deformity ◽  
Klippel Trenaunay Syndrome

Klippel–Trénaunay syndrome (KTS or KT) is an infrequently seen dermatological syndrome, which is often viewed as a triad of vascular malformation (capillary malformations or port-wine brands), venous varicosity, and soft tissue and/or bony hypertrophy. We report a case of a 12-year-old male who presented to us with the symptoms of varicose plaques over both lower limbs and was diagnosed as a case of KTS. Management is normally conservative and includes stockings for compression of the branches to reduce edema because of chronic venous insufficiency; modern devices that cause on and off pneumatic compression; and rarely, surgical correction of varicose veins with lifelong follow-up. The orthopedic abnormalities are treated with epiphysiodesis in order to prevent (stop) overgrowing of limb and correction of bone deformity.

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