glucuronyl-glucosamine-glycan-sulfate and Cardiovascular-Diseases

Since its introduction, sulodexide has been used on and off for several indications. More recently this agent has become revitalized and tested in newer indications. Sulodexide is composed of glycosaminoglycan that includes a mixture of fast-moving heparin and dermatan sulfate. It exerts its anticoagulant and antithrombotic action through interactions with both AT and HCII. Sulodexide has been proven to have effects on the fibrinolytic system, platelets, endothelial cells, inflammation and more recently metalloproteases. The administration of sulodexide results in the release of lipoprotein lipase and has been shown to reduce the circulating level of lipids. It has also shown to decrease the viscosity of both whole blood and plasma. Sulodexide differs from heparin in its oral bioavailability and longer half-life. There is also less bleeding associated with sulodexide. In addition, oral administration of sulodexide does not interfere with the pharmacologic actions of commonly used agents. Similar to heparin, sulodexide releases TFPI which contributes to its antithrombotic effect and anti-inflammatory properties. Sulodexide has been proven to be effective in peripheral arterial thrombosis and venous thrombosis. It is also clinically active in the treatment of venous leg ulcers and intermittent claudication. More recent data suggest that sulodexide can be used in tinnitus and in vascular vertigo. Additional studies in these indications are required. Sulodexide was generally safe and well tolerated in the clinical trials, without any severe bleeding complications. Therefore sulodexide appears to be a good treatment for all arterial and venous diseases and for the prevention of progression of disease.

Topics: Animals; Anti-Inflammatory Agents; Blood Coagulation; Cardiovascular Diseases; Drug Interactions; Fibrinolytic Agents; Glycosaminoglycans; Hemorrhage; Humans; Risk Assessment; Risk Factors

The glycocalyx is a jelly layer covering the endothelium constituted by glycosaminoglycans (GAGs), proteoglycans and adsorbed plasma proteins. This structure take part in several physiological and pathological vascular events. The glycocalyx acts as mechanosensor to shear stress and participates to regulation of vascular tone, permeability, coagulation and complement activation. Moreover it regulates the interaction and activation of blood cells with endothelial cells. The presence of a thick, normal glycocalyx is required for physiological vascular functions, whereas these functions are impaired by its damage by noxious agents. Indeed, glycocalyx alterations are involved in the pathogenesis of atherosclerosis, ischemia-reperfusion and diabetic vascular complications. GAGs such as sulodexide are promising agents to control endothelial dysfunction. They act at multiple levels: they promote glycocalyx reconstitution, control glycocalyx degrading enzymes, exert anti-inflammatory effects and have anti-apoptotic and anti-senescence effects on endothelial cells. Clinical studies support the evidence that glycosaminoglycans are useful to restore a normal endothelial function.

Topics: Animals; Anti-Inflammatory Agents; Cardiovascular Agents; Cardiovascular Diseases; Endothelium, Vascular; Glycocalyx; Glycosaminoglycans; Humans; Proteoglycans; Signal Transduction

Treatment of vascular diseases should be based on established pathophysiological concepts, and this also applies to chronic venous disease (CVD). On the basis of the latest research in this field, this paper summarizes the most advanced pathophysiological knowledge regarding the hemodynamics of the large veins and of the microcirculation, the endothelial function and inflammation, and the use of sulodexide in the treatment of CVD. The emerging theories on the pathophysiology of CVD consider inflammation, endothelial glycocalyx dysfunction, and the consequent changes in the extracellular matrix to play key roles in the development of CVD, and support a renewed interest in the research and application of sulodexide. As part of active approach to the treatment of CVD including edema and trophic venous alterations, sulodexide could help to alleviate progressive signs and symptoms of disease in any clinical CEAP class of CVD, from C1 to C6.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Glycosaminoglycans; Hemodynamics; Humans; Microcirculation; Treatment Outcome; Veins

This study was conducted to assess the efficacy of sulodexide, a glycosaminoglycan compound with antithrombotic properties, in preventing death and thromboembolic events after acute myocardial infarction.. Antithrombotic therapy has been found to play an important role in the prevention of cardiovascular events and death after acute myocardial infarction. Glycosaminoglycan-containing compounds, including sulodexide, show profibrinolytic and antithrombotic properties that render them suitable for use in patients after infarction.. A total of 3,986 patients who had recovered from acute myocardial infarction were randomized to receive either the standard therapy routinely administered at each study center, excluding antiplatelet and anticoagulant drugs (control group, 1,970 patients), or the standard therapy plus sulodexide (treated group, 2,016 patients). Between 7 and 10 days after the episode of acute myocardial infarction, sulodexide was administered as a single daily 600-lipoprotein-lipase-releasing unit (LRU) intramuscular injection for the 1st month, followed by oral capsules of 500 LRU twice daily. Patients were evaluated for > or = 12 months.. At the end of the study, 140 deaths (7.1%) were recorded in the control group and 97 (4.8%) in the sulodexide group (32% risk reduction, p = 0.0022, chi-square test). A total of 90 patients (4.6%) in the control group had a further infarction, compared with 66 (3.3%) in the sulodexide group (28% risk reduction, p = 0.035). Furthermore, a reduction in left ventricular thrombus formation (evaluated by echocardiography) was observed in the sulodexide group (n = 12; 0.6%), compared with values in the control group (n = 25; 1.3%) (53% risk reduction, p = 0.027). Sulodexide was well tolerated and devoid of significant adverse events. All significant results were confirmed by "actual treatment" analyses.. The study provides evidence that long-term therapy with sulodexide started early after an episode of acute myocardial infarction is associated with reductions in total mortality, rate of reinfarction and mural thrombus formation.

Topics: Aged; Cardiovascular Diseases; Cause of Death; Female; Glycosaminoglycans; Heart Diseases; Humans; Hypolipidemic Agents; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Recurrence; Thrombolytic Therapy; Thrombosis; Time Factors