Diosmin Alleviates Venous Injury and Muscle Damage in a Mouse Model of Iliac Vein Stenosis

Chronic venous disease (CVD) is a progressive inflammatory disease that increases in prevalence with age. Elucidating the underlying molecular mechanism of CVD development is essential for disease prevention and treatment. This study constructed a mouse model of iliac vein stenosis to explore the mechanism of the CVD disease progression, and diosmin was administered as a positive control (as recommended by clinical practice). The mouse model was established successfully with iliac vein stenosis, leading to the expansion of the intercellular space and venous leakage. Conversely, micronized diosmin showed a dose-dependent therapeutic effect for these manifestations. Concerning the mechanism, iliac vein stenosis caused an inflammatory response in veins, while diosmin suppressed this increase. Furthermore, RNA sequencing analysis indicated that diosmin significantly improved muscle function through actin filament organization and muscle contraction. These results indicated that the mouse model of iliac vein stenosis is a reliable model to study venous diseases. Furthermore, the dose-dependent therapeutic effect of diosmin on stenosis (without toxic side-effects) suggests greater protection against venous diseases at higher doses of diosmin.

Shear Stress Alterations Activate BMP4/pSMAD5 Signaling and Induce Endothelial Mesenchymal Transition in Varicose Veins

Chronic venous diseases, including varicose veins, are characterized by hemodynamic disturbances due to valve defects, venous insufficiency, and orthostatism. Veins are physiologically low shear stress systems, and how altered hemodynamics drives focal endothelial dysfunction and causes venous remodeling is unknown. Here we demonstrate the occurrence of endothelial to mesenchymal transition (EndMT) in human varicose veins. Moreover, the BMP4-pSMAD5 pathway was robustly upregulated in varicose veins. In vitro flow-based assays using human vein, endothelial cells cultured in microfluidic chambers show that even minimal disturbances in shear stress as may occur in early stages of venous insufficiency induce BMP4-pSMAD5-based phenotype switching. Furthermore, low shear stress at uniform laminar pattern does not induce EndMT in venous endothelial cells. Targeting the BMP4-pSMAD5 pathway with small molecule inhibitor LDN193189 reduced SNAI1/2 expression in venous endothelial cells exposed to disturbed flow. TGFβ inhibitor SB505124 was less efficient in inhibiting EndMT in venous endothelial cells exposed to disturbed flow. We conclude that disturbed shear stress, even in the absence of any oscillatory flow, induces EndMT in varicose veins via activation of BMP4/pSMAD5-SNAI1/2 signaling. The present findings serve as a rationale for the possible use of small molecular mechanotherapeutics in the management of varicose veins.

Varicose veins in adolescents: a prospective cohort study

The article describes the experience of diagnostics and treatment of chronic diseases of the veins of the lower extremities in 164 female patients.Objective. To study the results of diagnosis and treatment of varicose veins in adolescent and adult females.Patient characteristics and research methods. The authors carried out a prospective study, they analyzed health condition of a group of adolescents and examined this group in 5 years later (the adult part of the study). The authors used clinical examination for diagnostics (disease assessment according to CEAP classification), ultrasound examinations, telephone interviews. Re-examination of the patients showed good long-term results of treatment. There were no re-operations.Results. According to the data of a five-year follow-up, interventions were performed in 4 (4%) cases in the study group. The proportion of cured patients remained without significant changes.Conclusion. 1. Phlebology of childhood is characterized by the predominance of uncomplicated forms of varicose veins, with a simultaneous high concern about the disease of the patient and parents. 2. Timely surgical and laser interventions and the prescribed nonsurgical treatment program allow achieving a lasting improvement in the majority of patients with good long-term results. 3. Observation of patients with chronic venous diseases during their transition to the adult age group shows the preservation of good results in the majority of cases.

The aging venous system: from varicosities to vascular cognitive impairment

Aging-induced pathological alterations of the circulatory system play a critical role in morbidity and mortality of older adults. While the importance of cellular and molecular mechanisms of arterial aging for increased cardiovascular risk in older adults is increasingly appreciated, aging processes of veins are much less studied and understood than those of arteries. In this review, age-related cellular and morphological alterations in the venous system are presented. Similarities and dissimilarities between arterial and venous aging are highlighted, and shared molecular mechanisms of arterial and venous aging are considered. The pathogenesis of venous diseases affecting older adults, including varicose veins, chronic venous insufficiency, and deep vein thrombosis, is discussed, and the potential contribution of venous pathologies to the onset of vascular cognitive impairment and neurodegenerative diseases is emphasized. It is our hope that a greater appreciation of the cellular and molecular processes of vascular aging will stimulate further investigation into strategies aimed at preventing or retarding age-related venous pathologies.

Hemodynamic effects of combined antihypertensive therapy during exercise in men with arterial hypertension and chronic venous diseases

Introduction. Currently, there is insufficient data on the effect of modern antihypertensive therapy (AHT) on venous circulation, especially during physiological stress.Aim of the study – the investigation was to study the hemodynamic effects of a combination of a calcium channel blocker (CCB) and an angiotensin-converting enzyme (ACE) inhibitor during exercise in men with arterial hypertension (AH) and chronic venous diseases (CVD).Material and methods. In 46 men 30–50 years old with AH on the background of AHT, a comparative assessment of the dynamics of SBP, DBP, peripheral venous pressure (PVP), ultrasound parameters of venous blood flow of the left leg in response to physical activity (Ruffier’s test) was performed. The parameters were assessed in 23 patients with hypertension without CVD and 23 patients with hypertension and CVD. We studied the reaction before and after 14 days of combined AHT with the use of CCB (Amlodipine) and an ACE inhibitor (Lisinopril).Results. Before treatment, the response to exercise in patients of both groups was the same and was manifested by a twofold increase in the area of the lumen of the veins and a drop in blood flow velocity. Patients with CVD before treatment with exercise were characterized by an altered systemic hemodynamic response, more frequent cases of venous dilatation and decreased blood flow velocity. After AHT with exercise, both groups showed normalization and identity of SBP. DBP, PVP, a decrease in the severity of venous dilatation and a decrease in blood flow velocity. Patients with CVD after AHT in response to exercise are characterized by more pronounced venous dilatation and higher blood flow velocity.Conclusion. After 14 days of antihypertensive therapy in patients with hypertension without chronic venous disease and in patients with hypertension and chronic venous disease during exercise normalization of systolic blood pressure, diastolic blood pressure, PVP, a decrease in venous dilatation and a decrease in blood flow velocity are noted. Patients with CVD after AHT under load are characterized by varicose veins and accelerated venous blood flow.

Interrelation of venous and osteoarticular pathology in patients with Giacomini's vein

Objective: To establish a possible relationship between the Giacomini vein and osteoarticular pathology of the lower extremities in chronic venous diseases (CVD).Materials and methods. In 115 examined patients (out of 321), we identified the Giacomini vein (92 women, 23 men). The average age of men was 44.82 ± 1.62 years; women – 45.36 ± 3.31 years. All patients were divided into 3 groups by anatomical randomization. The first group was without pathology, the second group of patients had only CVD, and the third group included patients with CVD and osteoarticular pathology. The criteria for inclusion in the groups were: the presence of Giacomini vein in patients, chronic venous disease and osteoarticular pathology on one or both lower extremities. Exclusion criteria: age of patients less than 18 years, the presence of CVD C5-C6 according to the CEAP classification, post-traumatic changes in the osteoarticular system, post-thrombotic transformation of the veins of the lower extremities. Using triplex angioscanning, the anatomical features of the structure of the venous system of the lower extremities were assessed. The study of the condition of the foot was carried out using the Friedland method.Results. Group I with an absolute norm of the venous and osteoarticular systems included 30 people (26 %). The second group consisted of 45 patients (39.22 %) with CVD C0-C4 according to CEAP, and the third group consisted of 40 patients (34.78 %) who, in addition to venous, osteoarticular pathology. Chronic venous diseases in patients of groups II and III were distributed as follows: C0 – 25.6 %; C1 – 16.4 %; C2 – 49.4 %; C3 – 4.3 %; C4 – 4.3 % on the CEAP scale. Among the osteoarticular pathology, the most numerous group consisted of changes in the configuration of the foot, non-traumatic deformities – 32 (27.81 %) cases. To confirm the relationship between venous and osteoarticular pathology, we used the Pearson criterion. We found a significant correlation in the presence of nontraumatic deformities of the foot in the group of patients with CVD (Pearson's criterion 0.749642; p < 0.22). A strong correlation was established between the age of patients and changes in the venous and osteoarticular systems of the lower extremities (Pearson's criterion 0.7677696; p < 0.22), which confirms the relationship between the development of nontraumatic changes in the foot and CVD in patients with Giacomini vein with age.Conclusion. It was found that the presence of an altered Giacomini vein leads to an aggravation of venous stasis in the lower extremities, which in turn increases the likelihood of developing venous pathology. Chronic diseases of the veins of the lower extremities contribute to dystrophic changes in soft tissues, most pronounced in the distal part of the extremity and, as a consequence, predispose to the development of osteoarticular pathology.