Factors Influencing Venous Remodeling in the Development of Varicose Veins of the Lower Limbs.

One of the early symptoms of chronic venous disease (CVD) is varicose veins (VV) of the lower limbs. There are many etiological environmental factors influencing the development of chronic venous insufficiency (CVI), although genetic factors and family history of the disease play a key role. All these factors induce changes in the hemodynamic in the venous system of the lower limbs leading to blood stasis, hypoxia, inflammation, oxidative stress, proteolytic activity of matrix metalloproteinases (MMPs), changes in microcirculation and, consequently, the remodeling of the venous wall. The aim of this review is to present current knowledge on CVD, including the pathophysiology and mechanisms related to vein wall remodeling. Particular emphasis has been placed on describing the role of inflammation and oxidative stress and the involvement of extracellular hemoglobin as pathogenetic factors of VV. Additionally, active substances used in the treatment of VV were discussed.

Dystrophic Calcification of the Lower Leg in a Patient with Chronic Lower Extremity Venous Insufficiency and Diabetes Mellitus: A Case Report and Literature Review.

ABSTRACT: Chronic lower extremity venous insufficiency can cause local dystrophy, and some patients will develop calf dystrophic calcification. In this case report, the authors describe a patient with varicose veins of both lower extremities, venous insufficiency of the lower extremities, recurring ulcers on the left leg for more than 20 years, and diabetes mellitus with dystrophic calcification of the calf. The patient's left leg ulcer showed extensive chronic inflammation, pathological calcification, and necrosis of the subcutaneous tissue with a thickness of approximately 0.5 to 1 cm. The computed tomography, X-ray, and hematoxylin-eosin staining results confirmed calcification; the leg skin thickened because of inflammatory irritation. After 11 months of treatment, the calcified and necrotic calcification and necrotic tissue were removed, and the wound healed.

Abnormal proinflammatory and stressor environmental with increased the regulatory cellular IGF-1/PAPP-A/STC and Wnt-1/ß-Catenin canonical pathway in placenta of women with Chronic venous Disease during Pregnancy.

Lower limbs venous insufficiency refers to a wide variety of venous disorders grouped by the term of chronic venous disease (CVD). Hemodynamic and hormonal changes related to pregnancy period, may promote the development of CVD affecting approximately 1 in 3 women. It has been shown that the presence of this condition is associated with damage and placental suffering. Thus, taking IGF-1/PAPP-A/STC-2, inflammatory cytokines production, PI3K/Akt and Wnt/ ß-catenin pathways as a part of the alterations that occurs in the placenta due to CVD, the aim of this study will be to examine the main components of these pathways. Genic and protein expression of PAPP-A, STC-2, IGF-1, IRS-4 Wnt-1, ß-catenin, c-myc, Cyclin D1, IL-4/IL-6 and PI3K/Akt/mTOR pathway will be analysed through RT-qPCR and immunohistochemical techniques in women with CVD (n=62) and pregnant women without this condition (HC) (n=52). PAPP-A, IGF-1, IL-4, IL-6, IRS-4, PI3K, Akt, mTOR, Wnt-1, ß-catenin, c-myc and Cyclin D1 expression were found to be increased in women with CVD, whereas STC-2 were decreased in this group, compared to non-affected women. Our study has demonstrated that IGF-1/PAPP-A/STC-2 axis, PI3K/Akt and Wnt/ß-catenin pathways, along with c-myc, Cyclin D1 and inflammatory cytokines are altered in placenta women with CVD. These results extent the knowledge that CVD is associated to a placenta damage with abnormal tissue environment and cellular regulation.

Histopathological study of JNK in venous wall of patients with chronic venous insufficiency related to osteogenesis process.

Chronic venous insufficiency (CVI) is one of the most common vascular pathologies worldwide. One of the risk factors for the development of CVI is aging, which is why it is related to senile changes. The main trigger of the changes that occur in the venous walls in CVI is blood flow reflux, which produces increased hydrostatic pressure, leading to valve incompetence. The cellular response is one of the fundamental processes in vascular diseases, causing the activation of cell signalling pathways such as c-Jun N-terminal kinase (JNK). Metabolic changes and calcifications occur in vascular pathology as a result of pathophysiological processes. The aim of this study was to determine the expression of JNK in venous disease and its relationship with the role played by the molecules involved in the osteogenic processes in venous tissue calcification. This was a cross-sectional study that analyzed the greater saphenous vein wall in 110 patients with (R) and without venous reflux (NR), classified according to age. Histopathological techniques were used and protein expression was analysed using immunohistochemistry techniques for JNK and markers of osteogenesis (RUNX2, osteocalcin (OCN), osteopontin (OPN)). Significantly increased JNK, RUNX2, OCN, OPN and pigment epithelium-derived factor (PEDF) protein expression and the presence of osseous metaplasia and amorphous calcification were observed in younger patients (<50 years) with venous reflux. This study shows for the first time the existence of an osteogenesis process related to the expression of JNK in the venous wall.

Comparison Between Cyanoacrylate Embolization and Radiofrequency Ablation for Superficial Venous Incompetence: A Systematic Review and Meta-analysis.

BACKGROUND: Chronic venous disease is a debilitating condition involving great saphenous vein (GSV) incompetence. OBJECTIVE: To investigate the efficacy and effectiveness of cyanoacrylate embolization (CAE) versus radiofrequency ablation (RFA) in patients with incompetent GSVs. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane library were searched. The primary outcomes were the Venous Clinical Severity Score (VCSS), Aberdeen Varicose Vein Questionnaire (AVVQ), closure rate, and visual analog scale (VAS) for pain. RESULTS: This meta-analysis included 378 and 590 patients who underwent CAE and RFA, respectively. Cyanoacrylate embolization was comparable with RFA in VCSS (weighted mean difference [WMD] = -0.03, 95% confidence interval [CI]: -0.18 to 0.12, p = .686), AVVQ (WMD = -0.08, 95% CI: -0.38 to 0.21, p = .570), closure rate (odds ratio [OR] = 0.61, 95% CI: 0.18-2.01, p = .414), and VAS (standardized mean difference [SMD] = 0.24, 95% CI: -0.59 to 1.06, p = .523). There were no significant differences between CAE and RFA regarding the occurrence of phlebitis (OR = 1.22, 95% CI: 0.70-2.13, p = .479) and pigmentation (OR = 0.48, 95% CI: 0.18-1.31, p = .153), but CAE had a lower risk of ecchymosis (OR = 0.45, 95% CI: 0.25-0.81, p = .007) and paresthesia (OR = 0.16, 95% CI: 0.03-0.99, p = .049). CONCLUSION: Cyanoacrylate embolization and RFA demonstrated no significant differences in VCSS, AVVQ, closure rate, and pain score for patients with incompetent GSVs. Patients in the CAE group had a lower risk of ecchymosis and paresthesia compared with the RFA group.

Pregnancy-associated venous insufficiency course with placental and systemic oxidative stress.

The development of lower extremity venous insufficiency (VI) during pregnancy has been associated with placental damage. VI is associated with increased oxidative stress in venous wall. We have investigated potential disturbance/dysregulation of the production of reactive oxygen species (ROS) in placenta and its eventual systemic effects through the measurement of malondialdehyde (MDA) plasma levels in women with VI. A total of 62 women with VI and 52 healthy controls (HCs) were studied. Levels of nicotinamide adenine dinucleotide phosphate-oxidase 1 (NOX1), 2 (NOX2), inducible nitric oxide synthase (iNOS), endothelial (eNOS), poly(ADP-ribose) polymerase PARP (PARP) and ERK were measured in placental tissue with immunohistochemistry and RT-qPCR. Plasma and placental levels of MDA were determined by colorimetry at the two study times of 32 weeks of gestation and post-partum. Protein and gene expression levels of NOX1, NOX2, iNOS, PARP and ERK were significantly increased in placentas of VI. eNOS activity was low in both study groups, and there were no significant differences in gene or protein expression levels. Women with VI showed a significant elevation of plasma MDA levels at 32 weeks of gestation, and these levels remained elevated at 32 weeks post-partum. The MDA levels were significantly higher in placentas of women with VI. Placental damage that was found in the women with VI was characterized by overexpression of oxidative stress markers NOX1, NOX2, and iNOS, as well as PARP and ERK. Pregnant women with VI showed systemic increases in oxidative stress markers such as plasma MDA levels. The foetuses of women with VI had a significant decrease in their venous pH as compared to those from HC women. The situation of oxidative stress and cellular damage created in the placenta is in coexpression with the production of a pH acidification.

Role of fibronectin in chronic venous diseases: A review.

Fibronectin (FN) circulating in the blood and produced by cells provides the basis of the extracellular matrix (ECM) formed in healing acute wounds. The time-dependent deposition of FN by macrophages, its synthesis by fibroblasts and myofibroblasts, and later degradation in the remodeled granulation tissue are a prerequisite for successful healing of wounds. However, the pattern of FN expression and deposition in skin lesions is disturbed. The degradation of the ECM components including FN in varicose veins prevails over ECM synthesis and deposition. FN is inconspicuous in the fibrotic lesions in lipodermatosclerosis, while tenascin-C containing FN-like peptide sequences are prominent. FN is produced in large amounts by fibroblasts at the edge of venous ulcers but FN deposition at the wound bed is impaired. Both the proteolytic environment in the wounds and the changed function of the ulcer fibroblasts may be responsible for the poor healing of venous ulcers. The aim of this review is to describe the current knowledge of FN pathophysiology in chronic venous diseases. In view of the fact that FN plays a crucial role in organizing the ECM, further research focused on FN metabolism in venous diseases may bring results applicable to the treatment of the diseases.

Lipidomic profiling of chorionic villi in the placentas of women with chronic venous disease.

Background: Chronic venous disease (CVD) is a prevalent lower limb venous pathology that especially affects women, who also show an increased risk of this disease during pregnancy. Studies have shown significant structural changes in the placentas of women with CVD and several markers of tissue damage have been also described. Patients and Methods: To try to understand the different placental pathologies, research efforts have focused on examining metabolomic profiles as indicators of the repercussions of these vascular disorders. This study examines changes produced in the metabolomic profiles of chorionic villi in the placentas of women with CVD. In a study population of 12 pregnant women, 6 with and 6 without CVD, we compared through mass spectroscopy coupled to ultra-high performance liquid chromatography (UHPLC-MS), 240 metabolites in chorionic villus samples. Results: This study is the first to detect in the placental villi of pregnant women with CVD, modifications in lysophosphatidylcholines and amino acids along with diminished levels of other lipids such as triglycerides, sphingomyelins, and non-esterified omega 9 fatty acids, suggesting a role of these abnormalities in the pathogenesis of CVD. Conclusions: Our findings are a starting point for future studies designed to examine the impacts of CVD on maternal and fetal well-being.

Potential Role of Venular Amyloid in Alzheimer's Disease Pathogenesis.

Insurmountable evidence has demonstrated a strong association between Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA), along with various other cerebrovascular diseases. One form of CAA, which is the accumulation of amyloid-beta peptides (Aß) along cerebral vessel walls, impairs perivascular drainage pathways and contributes to cerebrovascular dysfunction in AD. To date, CAA research has been primarily focused on arterial Aß, while the accumulation of Aß in veins and venules were to a lesser extent. In this review, we describe preclinical models and clinical studies supporting the presence of venular amyloid and potential downstream pathological mechanisms that affect the cerebrovasculature in AD. Venous collagenosis, impaired cerebrovascular pulsatility, and enlarged perivascular spaces are exacerbated by venular amyloid and increase Aß deposition, potentially through impaired perivascular clearance. Gaining a comprehensive understanding of the mechanisms involved in venular Aß deposition and associated pathologies will give insight to how CAA contributes to AD and its association with AD-related cerebrovascular disease. Lastly, we suggest that special consideration should be made to develop Aß-targeted therapeutics that remove vascular amyloid and address cerebrovascular dysfunction in AD.

The comparative analysis of non-thrombotic internal jugular vein stenosis and cerebral venous sinus stenosis.

Internal jugular vein (IJV) stenosis and cerebral venous sinus (CVS) stenosis belong to cerebral venous outflow insufficiency. This study aimed to analyze the similarities and differences between IJV stenosis and CVS stenosis. Patients with either IJV stenosis or CVS stenosis confirmed by contrast-enhanced magnetic resonance venography between October 2017 and July 2018 were enrolled in this retrospective study. The similarities and differences between IJV stenosis and CVS stenosis on the aspects of clinical and imaging features were compared. A total of 82 eligible patients entered into the final analysis. The similarities of the two subsets of cerebral venous outflow insufficiency mainly included headache, head noises or tinnitus, visual disorders, and sleeping disorders, as well as cloud-like white matter hyperintensity in T2WI and FLAIR sequences of MRI. However, there were differences in between, the ratio of patients with higher intracranial pressure (ICP) was common in CVS stenosis (p < 0.001). Namely, higher ratios of papilledema (p = 0.001) and visual damage (p = 0.029), as well as poor Frisen papilledema grade scores were more commonly observed in CVS stenosis (p = 0.004), while abnormal collateral-vessels appeared more frequently in IJV stenosis (100.00%) than CVS stenosis (28.57%). Continuous head noises, tinnitus and cloud-like white matter hyperintensity in MRI are the features of both IJV stenosis and CVS stenosis. Whereas, severe headache, visual damage, papilledema, and intracranial hypertension (IH) were more common in CVS stenosis, and the appearance of collateral-vessels is a key feature of IJV stenosis.

The Morphofunctional Changes in the Wall of Varicose Veins.

BACKGROUND: Varicose vein (VV) disease is a frequently occurring pathology of the lower extremities. Although the pathogenesis of varicosity development is not clearly defined, the final common pathway leading to chronic venous insufficiency is the development of venous hypertension, which is associated with severe changes in the venous wall. The aim of this study was to clarify the histological and immunohistochemical changes in great saphenous veins (GSVs) in chronic venous insufficiency. METHODS: A histopathological study was conducted on 20 patients with VVs (4 males, 16 females) and 4 (1 male, 3 females) patients undergoing distal bypass surgery. Tissues were processed for histological routine straining and immunohistochemical studies of vascular endothelial growth factor (VEGF), intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, protein gene product 9.5 (PGP 9.5), and collagen type IV, laminin, and fibronectin. A semiquantitative evaluation method was used. RESULTS: Compared with the normal SV, VV sections showed the damaged endothelium areas, significant disorganization of the smooth muscle bundles, and highest density of the vasa vasorum in the tunica media and tunica adventitia, as well as sclerotic blood vessels and neoangiogenesis in almost all specimens. Immunohistochemistry study showed statistically significant difference between the VVs and the control group of several parameters, such as PGP 9.5 positive structures (P < 0.05; 1-tailed significance) and laminin positive structures in subendothelial layer of VVs (P < 0.05; 1-tailed significance). There is also the tendency in increasing of VEGF expression and decreasing of collagen IV structures. Our study did not show statistically significant difference in VEGF, ICAM-1, and VCAM-1 positive structures between varicose and normal veins; however, it could be explained by the limitations of the study. CONCLUSIONS: Varicose GSVs represent nonhomogeneous integrity of the basement membrane, smooth muscle disorganization, and active neoangiogenesis, suggesting remodulation of blood vessels. Changes in the appearance of PGP 9.5-containing innervation, laminin, and collagen IV in tunica intima confirm the remodulation of damaged blood vessels.

Genetic predisposition for chronic venous insufficiency in several genes for matrix metalloproteinases (MMP-2, MMP-9, MMP-12) and their inhibitor TIMP-2.

OBJECTIVE: The project was scheduled as a case-control study to investigate the correlation between MMP-2 (rs243864), MMP-9 (3918242), MMP-12 (rs7123600) and TIMP-2 (rs8176329) polymorphisms and chronic venous disease (CVD) risk. The genotype and phenotype research envisages the testing of possible associations between MMP and TIMP-2 genotypes and phenotypes of CVD. MATERIAL AND METHODS: 150 patients with CVD and 227 controls were enrolled into the study. The MMPs and TIMP-2 genotypes were identified by the PCR method and restriction analysis according to standard protocols. RESULTS: The G allele of MMP-2 -790 T/G was 1.85 times more frequent in men with CVD than in the control group (P = 0.008). The T allele of MMP-9 -1562 C/T was observed 2.571 times more frequently in patients with CVD than in the control individuals (both in men and women) with clinically significant specificity (P = 0.0000009). The G allele of MMP-12 rs7123600 was determined 2.082 times more frequently in female patients with CVD than in the control group with clinically significant specificity (P = 0.02). No significant result in TIMP-2 rs8176329 polymorphism in the case-control study was observed. CVD women with G allele in MMP-2 -790 T/G in the genotype-phenotype study are seen to develop ulceration 2.539 times more frequently (P = 0.003). The G allele of MMP-12 rs7123600 was detected 3.167 times more frequently in CVD women with ulceration compared with CVD women without ulceration (P = 0.007). In CVD men in C6 stage, the incidence of AG genotype in rs7123600 MMP-12 polymorphism was found to be 4.675 times higher compared to CVD women with C6 staging (P = 0.005). The AG genotype in TIMP 2 rs8176329 polymorphism was found to be associated with higher risk of tumour (P = 0.01). CONCLUSION: Studying these polymorphisms can contribute to better identification of patients at higher risk of developing CVD, while providing the most appropriate prevention and treatment strategies for limiting the progression and complications of CVD.

The Diagnosis and Management of Early Deep Vein Thrombosis.

The diagnosis and management of an acute DVT is difficult and mistakes are often made. The cost to the National Health Service (NHS) of litigation arising from failure to diagnose and treat DVT early is substantial. Clinical diagnosis alone is often unreliable and a large proportion of DVT occurring in hospital are asymptomatic. In the United Kingdom, clinical scoring systems, D-dimer and ultrasound (US) imaging have all been adopted to aid diagnosis via DVT pathways. These pathways aim to exclude DVT only and often fail to actually address the cause of the symptoms once DVT is eventually cleared.

Portal vein stent placement for the treatment of postoperative portal vein stenosis: long-term success and factor associated with stent failure.

BACKGROUND: Portal vein stenosis develops due to different causes including postoperative inflammation and oncological processes. However, limited effective therapy is available for portal vein stenosis. The objectives of this study were to evaluate the efficacy of a portal vein stent for portal vein stenosis after hepatobiliary pancreatic surgery and to determine the factors associated with stent patency. METHODS: From December 2003 to December 2015, portal vein stents were implanted in 29 patients who had portal vein stenosis after hepatobiliary pancreatic surgery. We conducted a retrospective analysis to evaluate the efficacy and safety of portal vein stent placement. Twelve clinical variables were analyzed for their role in stent patency. RESULTS: The symptoms before portal vein stent placements included nine patients with hepatic encephalopathy, six patients with gastrointestinal bleeding, four patients with ascites, and four patients with hyperbilirubinemia. Portal vein thrombosis due to postoperative portal stenosis was found in four patients. Portal vein stent were successfully implanted without any major complications. Of the 21 patients with symptoms, 17 showed improvement, and stent patency was maintained in 22 (76%) patients. The presence of a collateral vein is the only variable related to the development of an occlusion after portal stenting. CONCLUSION: Portal vein stent were implanted safely and had good long-term patency. This procedure is useful to relieve portal hypertension-related symptoms and to improve the quality of life. Our data strongly suggest that embolization to block blood flow in a collateral vein during portal vein stent placement will improve the patency of the stent.

TGF-ß1 in Vascular Wall Pathology: Unraveling Chronic Venous Insufficiency Pathophysiology.

Chronic venous insufficiency and varicose veins occur commonly in affluent countries and are a socioeconomic burden. However, there remains a relative lack of knowledge about venous pathophysiology. Various theories have been suggested, yet the molecular sequence of events is poorly understood. Transforming growth factor-beta one (TGF-ß1) is a highly complex polypeptide with multifunctional properties that has an active role during embryonic development, in adult organ physiology and in the pathophysiology of major diseases, including cancer and various autoimmune, fibrotic and cardiovascular diseases. Therefore, an emphasis on understanding its signaling pathways (and possible disruptions) will be an essential requirement for a better comprehension and management of specific diseases. This review aims at shedding more light on venous pathophysiology by describing the TGF-ß1 structure, function, activation and signaling, and providing an overview of how this growth factor and disturbances in its signaling pathway may contribute to specific pathological processes concerning the vessel wall which, in turn, may have a role in chronic venous insufficiency.

[CHANGES OF PH AND CYTOLOGICAL PICTURE AT VARIOUS STAGES OF WOUND HEALING IN PATIENTS WITH VENOUS GENESIS TROPHIC ULCERS OF THE LOWER LIMBS].

The analysis of 82 patients medical records with venous trophic ulcers (VTU) of the lower limbs were presenting. pH in patients with VTU determined in three locations: the surface of ulcers, venous modified and unmodified skin and ulcers. Cytological examination of secretions from wounds conducted in 32 (39.1%) patients using smears. In 19 (23.2%) patients prevailed exudation stage, in 37 (45.1%) ­ granulation, in 26 (31.7%) - epithelialization. At all stages of wound healing at a distance from the ulcers observed values change skin pH to the acid side. Typical sings of first phase of wound healing were degenerative­inflammatory and inflammatory type of cytogram, and for the granulation phase ­ inflammatory­regenerative and regenerative one.

Ultrasonography of Skin Changes in Legs with Chronic Venous Disease.

BACKGROUND: In daily practice, ultrasonography (US) is used only to designate the location and pattern of venous lesions. Skin US is not performed between routine venous investigations. METHODS: Skin morphology is evaluated by the same probes used for routine Duplex evaluation of superficial veins. US findings from evident skin lesions are comparatively evaluated with those from the surrounding apparently normal skin and from the contralateral leg. RESULTS: Inflammation and dermal edema can be found in the apparently normal skin of C2 legs. Swollen legs show thickening of the subcutaneous layer as a result of diffuse soaking or anechoic cavities, with or without dermal edema. Chronic hypodermitis is characterized by inflammatory edema in initial phases, and by liposclerosis in advanced cases. Recrudescence of inflammation provokes focal rarefactions of the subcutaneous layer, possibly related to ulcer opening. CONCLUSION: In legs with venous disorders, sonography refines clinical evaluation of the skin and may reveal changes not highlighted by inspection. Some of these changes could require further investigation because they have not yet been explained or described. Skin sonography should improve knowledge of the natural history of skin changes, as well as contribute to a better grading of venous diseases severity In particular, US evidence of cutaneous and subcutaneous changes in C2 legs should be considered to stratify the treatment in C2 legs, by identifying those in which varicose veins are not simply a cosmetic problem.

Endovascular radiofrequency ablation. Effect on the vein diameter using the ClosureFast(®) catheter. / Ablación endovascular por radiofrecuencia. Efecto sobre el diámetro venoso con el uso del catéter ClosureFast(®).

INTRODUCTION: Endovascular radiofrequency with first generation catheters was not successful due to its technical difficulty and restrictions in veins with diameters larger than 12mm. However, using the new catheter there is not enough scientific evidence to affirm that the diameter represents a technical limitation. The aim of this study was to evaluate and compare pre and post-operative venous trunks diameter, aiming at the reduction of size after 6 months with last generation catheters. METHODS: Retrospective observational and descriptive study on a cohort of patients with insufficiency of the great saphenous vein, small saphenous vein and anterior accessory vein operated on with last generation radiofrequency catheters. The diameters were evaluated in the pre and post-operative period with ultrasound. RESULTS: Between 2007 and 2014 a total of 365 ablations were performed in veins with an average diameter of 9±3.1mm showing a reduction of it after 6 months with a mean value of 5.2±0.8mm (P<.0001). Total occlusion was also observed in 100% of cases and complications such as deep vein thrombosis in 0.5% and heat-induced thrombosis in 1.1%. CONCLUSIONS: A significant reduction in venous diameter after endovascular treatment with the new ClosureFast(®) catheters was checked, even in veins with diameters greater than 12mm.

[Concentration of matrix metalloproteinases and magnesium ions in patients with varicose veins of lower limbs]. / Kontsentratsiya matriksnykh metalloproteinaz i ionov magniya pri varikoznoi bolezni ven nizhnikh konechnostei.

The study was aimed at investigating alterations in the concentration of matrix metalloproteinases (MMP-1, MMP-9) and the tissue inhibitor of metalloproteinase-1 (TIMP-1), as well as the level of magnesium ions (Mg2+) as an indicator of connective tissue dysplasia (CTD) in patients presenting with lower limb varicose veins. The study included a total of 110 people. Of these, the Study Group comprised 90 patients with lower limb varicose veins of clinical class C2-C6 (according to the CEAP classification) and the Control Group was composed of 20 apparently healthy volunteers. Samples of peripheral blood were examined. The content of MMP-9, MMP-1 and TIMP-1 in blood serum was determined by means of the quantitative solid-phase immunoenzymatic assay. The concentration of Mg2+ was determined by the colorimetric method. We revealed a statistically significant interrelationship between the concentrations of matrix metalloproteinases and severity of varicose transformation of lower-limb veins, with the highest level of matrix metalloproteinases being observed in patients with cutaneous alterations and trophic ulcers. Determination of the level of matrix metalloproteinases and magnesium ions, characterizing connective tissue dysplasia, makes it possible to predict the development of lower limb chronic venous insufficiency and to evaluate the degree of its severity.