chondroitin-sulfates and Aortic-Valve-Stenosis

Calcific aortic valve disease (CAVD), has been characterized as a cascade of cellular changes leading to leaflet thickening and valvular calcification. In diseased aortic valves, glycosaminoglycans (GAGs) normally found in the valve spongiosa migrate to the collagen I-rich fibrosa layer near calcified nodules. Current treatments for CAVD are limited to valve replacement or drugs tailored to other cardiovascular diseases.. Porcine aortic valve interstitial cells and porcine aortic valve endothelial cells were seeded into collagen I hydrogels of varying initial stiffness or initial stiffness-matched collagen I hydrogels containing the glycosaminoglycans chondroitin sulfate (CS), hyaluronic acid (HA), or dermatan sulfate (DS). Assays were performed after 2 weeks in culture to determine cell gene expression, protein expression, protein secretion, and calcification. Multiple regression analyses were performed to determine the importance of initial hydrogel stiffness, GAGs, and the presence of endothelial cells on calcification, both with and without osteogenic medium.. High initial stiffness hydrogels and osteogenic medium promoted calcification, while for DS or HA the presence of endothelial cells prevented calcification. CS was found to increase the expression of pro-calcific genes, increase activated myofibroblast protein expression, induce the secretion of collagen I by activated interstitial cells, and increase calcified nodule formation.. This study demonstrates a more complete model of aortic valve disease, including endothelial cells, interstitial cells, and a stiff and disease-like ECM. In vitro models of both healthy and diseased valves can be useful for understanding the mechanisms of CAVD pathogenesis and provide a model for testing novel therapeutics.

Topics: Animals; Aortic Valve; Aortic Valve Stenosis; Calcinosis; Cells, Cultured; Chondroitin Sulfates; Collagen; Endothelial Cells; Glycosaminoglycans; Hydrogels; Swine

Topics: Aged, 80 and over; Anticoagulants; Aortic Valve Stenosis; Chondroitin Sulfates; Dermatan Sulfate; Echocardiography, Transesophageal; Female; Fibrinolytic Agents; Heart Valve Prosthesis; Heparin; Heparitin Sulfate; Humans; Middle Aged; Thrombocytopenia; Thrombosis; Tomography, X-Ray Computed

Heparin is the standard anticoagulant for patients undergoing cardiopulmonary bypass. There are some patients for whom heparin is unsuitable and ancrod (a defibrinogenating enzyme) has been used as an alternative. We present a patient with heparin-induced thrombocytopenia in whom treatment ancrod was ineffective. The addition of danaparoid sodium (a heparinoid) allowed safe cardiopulmonary bypass. We discuss the reasons for this and suggest that the combination of ancrod and danaparoid sodium is a logical one in such cases.

Topics: Ancrod; Anticoagulants; Aortic Valve Stenosis; Cardiopulmonary Bypass; Chondroitin Sulfates; Coronary Disease; Dermatan Sulfate; Drug Combinations; Drug Therapy, Combination; Female; Heparin; Heparinoids; Heparitin Sulfate; Humans; Middle Aged; Thrombocytopenia

The 29-year-old, heroin-addicted patient received an aortic valve prosthesis (SJM) 10 years ago because of aortic valve stenosis III. One year after surgical treatment he refused to take Phenprocoumon and thus received no anticoagulation for 9 years. The patient was hospitalized due to cardial decompensation and thrombosis of the aortic valve prosthesis was diagnosed. Under heparinization, he developed heparin-induced thrombocytopenia type II, which disappeared after changing the medication to Danaparoid-Sodium. In order to avoid any further heparin exposure, we also carried out the surgical replacement of the aortic valve prosthesis under anticoagulation with Danaparoid-Sodium.

Topics: Adult; Aortic Valve Stenosis; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Heart Valve Prosthesis; Heparin; Heparitin Sulfate; Heroin Dependence; Humans; Male; Platelet Count; Postoperative Complications; Prosthesis Failure; Reoperation; Thrombocytopenia; Thrombosis

Topics: Adolescent; Aortic Valve Stenosis; Child; Chondroitin Sulfates; Dental Enamel Hypoplasia; Face; Female; Glycosaminoglycans; Growth Disorders; Humans; Joint Diseases; Male; Syndrome; Voice