fondaparinux and Atherosclerosis

Antithrombotic medication can be performed by means of heparins (non-fractionated heparin, low molecular heparins) or the pentasaccharide Fondaparinux as well as with oral vitamin K antagonists. The use of a low molecular heparin is initially recommended for the sake of practicability and safety in case of patients suffering from deep venous thrombosis of the leg and pelvis with subsequent long-term oral medication using a vitamin K antagonist (Marcumar) for anticoagulation. The most frequent indications for long-term anticoagulation are deep leg and pelvis thromboses, pulmonary embolism with atrial fibrillation, artificial prosthetic valves and open oval foramen with ischaemic cerebral infarction. In case of patients with chronic atrial fibrillation it is expedient to initiate permanent anticoagulation according to a risk score. For the purpose of controlling oral anticoagulation it is recommended to employ the INR value in place of Quick's value because these data are better comparable. In case of atherothrombotic diseases secondary prevention will always indicate administration of a thrombocyte aggregation inhibitor. In such cases acetylsalicylic acid is recommended as the standard preparation.

Topics: Administration, Oral; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atherosclerosis; Atrial Fibrillation; Blood Coagulation Tests; Cerebral Infarction; Drug Therapy, Combination; Female; Fibrinolytic Agents; Fondaparinux; Heart Valve Prosthesis; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Phenprocoumon; Platelet Aggregation Inhibitors; Polysaccharides; Preoperative Care; Prevalence; Primary Prevention; Pulmonary Embolism; Risk Factors; Sex Factors; Stroke; Time Factors; Venous Thrombosis

Atherosclerosis is a progressive inflammatory disease that can lead to sudden cardiac events by plaque rupture and subsequent thrombosis. Factor Xa (FXa) not only occupies a crucial position in the coagulation cascade responsible for thrombin generation, but also has pro-inflammatory effects. The hypothesis that Fondaparinux, the selective FXa inhibitor, attenuates plaque progression and promotes stability of atherosclerotic lesions was assessed.. Fondaparinux (5 mg/kg body weight/day) or 0.9% saline was intraperitoneally administered for 4 weeks to apolipoprotein E-deficient mice (n=12 per group) with established atherosclerotic lesions in the innominate arteries. Fondaparinux did not remarkably decrease the progression of atherosclerosis development in apolipoprotein E-deficient mice, but increased the thickness of fibrous cap (P=0.049) and decreased the ratio of necrotic core (P=0.001) significantly. Moreover, Fondaparinux reduced the staining against Mac-2 (P=0.017), α-SMA (P=0.002), protease-activated receptor (PAR)-1 (P=0.001), PAR-2 (P=0.003), CD-31 (P=0.024), MMP-9 (P=0.000), MMP-13(P=0.011), VCAM-1 (P=0.041) and the mRNA expression of inflammatory mediators (P<0.05) significantly, such as interleukin (IL)-6, MCP-1, IFN-γ, TNF-α, IL-10 and Egr-1.. Fondaparinux, the selective FXa inhibitor, can promote the stability of atherosclerotic lesions in apolipoprotein E-deficient mice, possibly through inhibiting expression of the inflammatory mediators in plaque and reduced synthesis of MMP-9 and MMP-13.

Topics: Animals; Apolipoproteins E; Atherosclerosis; Blood Coagulation; Brachiocephalic Trunk; Cytokines; Disease Models, Animal; Disease Progression; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Fibrosis; Fondaparinux; Inflammation Mediators; Male; Matrix Metalloproteinase 13; Matrix Metalloproteinase 9; Mice, Knockout; Necrosis; Plaque, Atherosclerotic; Polysaccharides; Time Factors

Topics: Animals; Apolipoproteins E; Atherosclerosis; Brachiocephalic Trunk; Factor Xa Inhibitors; Fondaparinux; Male; Polysaccharides