The Role of Endothelial Dysfunction and Inflammation in Chronic Venous Disease

Castro‐Ferreira, Ricardo; Cardoso, Rita Alves de Almeida; Leite‐Moreira, Adelino F.; Mansilha, Armando

doi:10.1016/j.avsg.2017.06.131

Cited by 140 publications

(115 citation statements)

References 116 publications

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“…Chronic venous disease (CVD)-in the more advanced stages also referred to as chronic venous insufficiency or CVI-is a multifactorial condition of the lower limbs related to endothelial dysfunction, inflammation, vein wall remodelling, incompetent valves, venous hypertension and reflux [1]. Other causes include venous outflow obstruction and failure of the calf muscle pump owing to obesity or leg immobility [2].…”

Section: Introductionmentioning

confidence: 99%

Sulodexide for the Symptoms and Signs of Chronic Venous Disease: A Systematic Review and Meta-analysis

Bignamini

Matuška²

2020

Adv Ther

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Introduction: Chronic venous disease (CVD) is a common condition associated with valvular dysfunction, venous hypertension and endothelial inflammation. Sulodexide facilitates the healing of venous ulcers and is frequently used in patients with CVD without ulcer. This review assessed the efficacy and safety of sulodexide for treatment of signs and symptoms of lower extremity CVD. Methods: We searched MEDLINE, EMBASE, CINAHL and AMED as well as the Cochrane Central Register of Controlled Trials and the World Health Organisation (WHO) International Clinical Trials Registry Platform Search Portal. We also manually searched potentially relevant journals, conference proceedings and journal supplements. Any study monitoring any effect of sulodexide in patients with CVD at any stage of the disease, classified or non-classified, was considered. Treatment effects were estimated using standardised mean differences (SMDs), mean differences (MDs) and risk ratios (RRs), as appropriate. We calculated 95% confidence intervals (CIs) and heterogeneity (Q, tau and I 2 ). Results: The search found 64 studies, but only 23 provided data on 7153 participants (mean age 55 years; 68% female). The 13 studies providing extractable quantitative information included 1901 participants (mean age 55.2 years; 65% female). Sulodexide decreased the intensity of pain, cramps, heaviness, oedema and total symptom score and reduced inflammatory mediators in patients with CVD. The risk of adverse events (AEs) was not different between sulodexide and placebo or heparan sulphate (RR 1.31, 95% CI 0.74-2.32; I 2 = 0%; 270 participants). The overall risk of AEs with sulodexide was low: 3% (95% CI 1-4%) estimated from 3656 participants. Conclusion: Sulodexide was found to have a beneficial venoactive effect on the major signs and symptoms of CVD such as pain, cramps, heaviness and oedema without increasing the risk of AEs. It is also likely to exert a systemic effect on the course of CVD by interfering with inflammatory chemokines. Key Summary PointsThe majority of validated approaches for the management of chronic venous disease (CVD) are relatively invasive and may be limited by patient acceptance; compression is instead usually associated with poor compliance.This systematic review assessed the efficacy and safety of sulodexide for treatment of signs and symptoms of lower extremity CVD by reviewing the literature and conducting a meta-analysis.Sulodexide had a beneficial venoactive effect on the major signs and symptoms of CVD, such as pain, cramps, heaviness and oedema, without increasing the risk of adverse events. It is also likely to exert a systemic effect on the course of CVD by interfering with inflammatory chemokines.

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Section: Introductionmentioning

confidence: 99%

Sulodexide for the Symptoms and Signs of Chronic Venous Disease: A Systematic Review and Meta-analysis

Bignamini

Matuška²

2020

Adv Ther

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“…The increase in venous pressure also increases the tension of the endothelial wall, which stimulates the production and activity of MMPs. Increased venous pressure also causes loss of endoluminal glycosaminoglycans (GAGs glycocalyx), endothelial cell lesions, resulting in increased vascular permeability, leukocyte infiltration and increased adhesion molecules (ICAM-1, VCAM-1, L-selectin, P-selectin) inflammatory cytokines and reactive oxygen species (ROS) with the end result of a further increase in MMPs 7,8 .…”

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confidence: 99%

“…Increase in MMPs can also cause hyperpolarization and relaxation of the smooth muscle cells (VSM) and ECM degradation, leading to dilatation of the venous wall, valve dysfunction and to the progressive increase of venous hydrostatic pressure, thus establishing, an actual vicious circle of hemodynamic and inflammatory self-feeding. The formation of varicose veins and their tortuosity is also favored by the action of MMPs, which degrade the extracellular matrix in particular in the atrophic regions [5][6][7][8] .…”

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confidence: 99%

“…MMPs can interact with bioactive molecules on the cell membrane and regulate cellular receptors and signaling, influencing cell proliferation, migration and differentiation, thus being directly involved also in cell apoptosis, immune response, tissue repair and in angiogenesis 6,7 .…”

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confidence: 99%

“…Among the many pathophysiologic mechanisms at work, the leukocyte-endothelium interactions seem to be important in many aspects of the disease and have been identified as a possible target for pharmacologic intervention. Pharmacologic agents that could attenuate various elements of the inflammatory cascade and inhibit the inflammatory process might offer a greater opportunity to prevent future morbidity 6,7 . It seems reasonable to speculate that such treatment could reduce the risk of CVD progression if applied as soon as the first symptoms appear.…”

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confidence: 99%

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