scholarly journals Implication of the PI3K/Akt/mTOR Pathway in the Process of Incompetent Valves in Patients with Chronic Venous Insufficiency and the Relationship with Aging

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Miguel A. Ortega ◽  
Ángel Asúnsolo ◽  
Javier Leal ◽  
Beatriz Romero ◽  
María J. Alvarez-Rocha ◽  
...  

Chronic venous insufficiency (CVI) is a multifactorial disease, commonly caused by valvular incompetence (clinically diagnosed by venous reflux) and venous hypertension. The incidence of these factors clearly increases with patient age, and aging is one of the risk factors involved. The activity of the PI3K/Akt/mTOR pathway is considered fundamental in vascular pathologies, and understanding its involvement would help in the development of possible therapeutic targets. This is an observational, analytical, and prospective cohort study that reviewed 110 patients with CVI scheduled to undergo stratified saphenectomy. They were distributed according to the presence (R=81) or absence (NR=29) of valvular incompetence (venous reflux) diagnosed clinically. Each of the groups was further divided according to age, with a cutoff point of 50 years (NR<50=13, NR≥50=16, R<50=32, and R≥50=49). The involvement of the PI3K/Akt/mTOR pathway, as well as that of HIF-1α and HIF-2α and of CD4+, CD8+, and CD19+ cells and mastocytes, was assessed. Saphenous vein tissue samples obtained during surgery were processed for RT-qPCR and immunohistochemistry. Patients with venous reflux showed a significant increase in mRNA and protein expression levels for PI3K/mTOR and HIF-1α/HIF-2α. The number of mast cells was significantly elevated in the R group. In distribution by age, PI3K/Akt/mTOR and HIF-1α were significantly higher in R<50 patients. Furthermore, these patients had a significant increase in the number of CD4+, CD8+, and CD19+ cells and mastocytes in the saphenous vein wall. These findings provide a basis for the possible existence of changes in PI3K/Akt/mTOR pathway expression in young patients, with potential accelerated asynchronous aging that is enhanced by CVI.

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Miguel A. Ortega ◽  
Beatriz Romero ◽  
Ángel Asúnsolo ◽  
Mayte Sola ◽  
María J. Álavrez-Rocha ◽  
...  

Chronic venous insufficiency (CVI) is a disease that impacts cellular homeostasis. CVI may occur with a valvular destruction process known as venous reflux or valvular incompetence. One of the cellular processes that may be triggered as a consequence of these events is the production of reactive oxygen species (ROS), which may trigger the production of different cellular markers and cell damage processes, such as lipid peroxidation. Therefore, the present study performed an observational, analytical, and prospective cohort study by reviewing 110 patients with CVI, and the activities and plasma levels of iNOS, eNOS, NOX1, and NOX2 were determined using immunohistochemistry and RT-qPCR. Lipid peroxidation (MDA) was also measured. Patients were distributed according to the presence or absence of valvular incompetence-venous reflux, which was diagnosed clinically as the absence of venous reflux (NR=29) or presence of venous reflux (R=81). Each group was divided according to age, with a cutoff point of fifty years (NR<50=13, NR≥50=16, R<50=32, and R≥50=49). The results showed that R patients exhibited significantly increased plasma MDA levels, and R<50 patients exhibited the highest statistically significant increase. iNOS, NOX1, and NOX2 exhibited the highest gene and protein expression in R patients. The increased expression was maintained in the R<50 patients. Our data suggest that young patients with valvular incompetence (venous reflux) show higher levels of lipid peroxidation and oxidative stress, which reflects the characteristics of an aged patient.


Author(s):  
E.G. Cherkasheninov ◽  
A.S. Kalmykova

From 2015 to 2019, we performed surgical treatment of 136 patients for varicose veins of the lower extremities, of whom 74 patients were operated on by endovenous laser coagulation, 62 patients were operated on by radiofrequency ablation. The international classification of chronic venous insufficiency (CEAP) was used to distribute patients according to the severity of the disease. The indication for minimally invasive techniques was the presence of vertical reflux along the major and/or minor saphenous vein in combination with horizontal venous reflux in 95 % of cases. To perform radiofrequency ablation, the VNUS ClosureFast technique was used, and to perform endovasal laser obliteration, the «Lika-Hirurg» apparatus generating a wavelength of 1470 nm and radial (circular) light guides. To assess the results and quality of treatment, all patients underwent examination by a doctor with USDG of the operated lower extremity 1, 6 and 12 months after the treatment. Patients completed the Chronic Venous Insufficiency Questionnaire (CIVIQ 20) before surgery and 6 months after treatment. In all 136 patients, pathological venous reflux was not observed. In 2 patients, 6 months after EVLK, when performing ultrasound control in the trunks of the great saphenous vein, segmental recanalization without pathological reflux was determined. The use of radiofrequency ablation and endovasal laser coagulation of veins in the treatment of varicose veins shows positive results, and in most cases better than in classical surgical interventions, which is primarily due to the low trauma. One of the factors is the short duration of the patient's stay in the clinic and its activation immediately after the operation, which allows maintaining the routine of daily life.


Vascular ◽  
2021 ◽  
pp. 170853812110296
Author(s):  
Mustafa Aldemir ◽  
Ahmet Yuksel ◽  
Mehmet Inanir ◽  
Salih Metin ◽  
Yusuf Velioglu ◽  
...  

Objective Platelet distribution width (PDW) has been reported in a wide range of pathological settings. In this study, we aimed to investigate the relationship between PDW and lower extremity chronic venous insufficiency (CVI) by comparing the levels of PDW and other parameters derived from complete blood count (CBC) tests in young individuals with or without lower extremity CVI. Methods This prospective clinical study was conducted between January 2020 and December 2020. A total of 108 patients, 72 patients with lower extremity CVI (study group) and 36 healthy volunteers (control group) were enrolled from the Bursa Yuksek Ihtısas Educatıon Research Hospıtal and the Bolu Abant Izzet Baysal University Training and Research Hospital. The age range of the participants was between 18 and 50 years old. Participants’ baseline clinical features and CBC parameters including PDW, white blood cell, hemoglobin, hematocrit, mean corpuscular volume, red cell distribution width, neutrophil, lymphocyte, platelet count, mean platelet volume, plateletcrit, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were compared between the two groups. Results The groups were statistically similar in terms of baseline clinical features. The median PDW value was significantly higher for the CVI patients relative to the control group (17.6 vs 16.8; p < 0.001). In terms of other CBC parameters, there were no significant differences between the groups. According to ROC analysis, area under the curve of PDW was 0.749 (95% confidence interval: 0.653–0.846 and p < 0.001). If the value of PDW was accepted as 17, it could predict CVI with 76% sensitivity and 59% specificity, whereas a PDW value of 17.5 could predict CVI with 51% sensitivity and 81% specificity. Conclusion Platelet distribution width might be a useful marker to determine an increased inflammatory response and thrombotic status in young patients with CVI.


Angiology ◽  
2001 ◽  
Vol 52 (3_suppl) ◽  
pp. S23-S27 ◽  
Author(s):  
L. Incandela ◽  
G. Belcaro ◽  
M.R. Cesarone ◽  
M.T. De Sanctis ◽  
M. Griffin

Microcirculatory changes in chronic venous insufficiency (CVI) due to venous hypertension produce venous hypertensive microangiopathy (VHM) and lead to ulceration. VHM is charac terized by enlarged, convoluted capillaries; increase in flux, permeability, and edema; and altered microlymphatics. PO2 is decreased and CO2 increased. Capillary exchanges are altered and nutritional alterations in association with microtrauma may cause venous ulcers. The aim of this pilot, cross-over, randomized, placebo-controlled study was to evaluate the effect of local treatment with Essaven gel (EG) (single acute application) in 10 subjects with VHM and venous ulcers. The study was structured over 3 days: day 1 was used for the control evalua tion for all patients. One group was randomized for the sequence placebo (day 2) and EG the following day; the second group with the sequence EG (day 2) and placebo (day 3). Indepen dently from the sequence, measurements of flux and PO2 in standard conditions showed positive changes (significant decrease of the abnormally increased flux, PO2 increase) in the EG treatment group. Changes in the placebo group were limited and associated with skin manip ulation. In conclusion, EG acutely improves microcirculation in limbs with VHM and ulceration even with a single application.


Author(s):  
F. Kh. Nizamov

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.


2019 ◽  
Vol 3 (3) ◽  
pp. 09-12
Author(s):  
Dr. Ali Sapmaz ◽  
Dr. Serhan Yilmaz ◽  
Dr. Murat Özgür Kiliç ◽  
Dr. Betül Keskinkılıç Yağiz ◽  
Dr. Ahmet Serdar Karaca ◽  
...  

2010 ◽  
Vol 40 (3) ◽  
pp. 399-402 ◽  
Author(s):  
B. Kanchanabat ◽  
Y. Wongmahisorn ◽  
W. Stapanavatr ◽  
P. Kanchanasuttirak ◽  
A. Manomaiphiboon

2000 ◽  
Vol 15 (2) ◽  
pp. 64-70 ◽  
Author(s):  
J. Buján ◽  
F. Jurado ◽  
M. J. Gimeno ◽  
N. García-Honduvilla ◽  
G. Pascual ◽  
...  

Objective: An evaluation of the proteoglycan perlecan, collagen I and III, and metalloproteinases MMP−1, −2, −3 and −9 was performed to explore the possible relationships between ageing, affected vein region and reactive state of the varicose vein wall. Methods: Segments of saphenous vein were obtained from healthy subjects and from those with varicose veins. The vein specimens were subdivided according to subject age (<50/^50) and vein source (distal/proximal). Results: The walls of control vein specimens acquired a more collagenous appearance with age. These changes were not accompanied by significant modifications in the immunohistochemical markers used. In specimens from young patients, proximal varicose vein segments showed an increase in MMP-1, MMP-2 and MMP-9 expression. Subjects of more advanced age showed an increase in perlecan expression. Conclusion: This increase in MMPs could lead to the acceleration of the final fibrosclerotic process characteristic of the varicose vein wall.


2016 ◽  
Vol 32 (5) ◽  
pp. 334-341 ◽  
Author(s):  
Pedro Serralheiro ◽  
Elisa Cairrão ◽  
Cláudio J Maia ◽  
Marina João ◽  
Carlos M Costa Almeida ◽  
...  

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.


Angiology ◽  
2005 ◽  
Vol 56 (6_suppl) ◽  
pp. S21-S24 ◽  
Author(s):  
John J. Bergan

Chronic venous insufficiency is linked to venous hypertension and forces of shear stress on the endothelium. Venous hypertension depends upon two forces: the weight of a column of blood from the right atrium transmitted through the valveless vena cava and iliac veins to the femoral vein, and pressure generated by contracting skeletal muscles of the leg transmitted through failed perforating veins. When valve failure occurs in superficial axial veins and perforating veins, the venous pressure in the veins and venules of the skin and subcutaneous tissue is raised. The skin changes in chronic venous insufficiency are directly related to the severity of the venous hypertension. Also, pathologic changes in the valves are linked to venous hypertension and leukocyte infiltration and activation. It is hypothesized that acute venous pressure elevations cause a shift in the venous hemodynamics with changes in wall shear stress. This initiates the inflammatory cascade. Daflon 500 mg ameliorates the effects of chronic inflammation. In randomized trials, 60 days of therapy with Daflon at a dosage of 500 mg 2 tablets daily was effective, in addition to elastic compression, in accelerating venous ulcer healing. Because venous insufficiency is linked to venous hypertension and an inflammatory reaction, it appears that Daflon 500 mg 2 tablets daily shows a great potential for accomplishing blockade of the inflammatory cascade.


Sign in / Sign up

Export Citation Format

Share Document