chondroitin-sulfates and Aortic-Aneurysm--Abdominal

Deficient healing after endovascular aneurysm repair with a stent-graft is thought to be related to pro-apoptotic environment in abdominal aortic aneurysms and inertness of graft materials. We developed a bioactive coating containing chondroitin-4-sulfate and assessed its potential to improve cell adhesion, viability and resistance to apoptosis on PET surfaces. Coatings of collagen type I and CS were prepared and characterized by DMMB, FT-IR, DSC, SEM and contact angle goniometry. Preliminary cell culture experiments with vascular smooth muscle cells showed increased adhesion and viability in serum-free medium on CS-coated surfaces compared to control PET films.

Topics: Animals; Aortic Aneurysm, Abdominal; Apoptosis; Blood Vessel Prosthesis; Blood Vessels; Cell Adhesion; Cell Culture Techniques; Cell Line; Cell Survival; Chondroitin Sulfates; Coated Materials, Biocompatible; Collagen Type I; Humans; Materials Testing; Methylene Blue; Muscle, Smooth, Vascular; Polyethylene Terephthalates; Rats; Spectroscopy, Fourier Transform Infrared; Stents; Wound Healing

Chronic disseminated intravascular coagulation (DIC) is a well-known complication of aortic aneurysm. A 63-year-old man with bleeding tendency and a large palpable abdominal aortic aneurysm (AAA) was diagnosed as having fibrinolysis dominant DIC by the excessive activation of both coagulation and fibrinolysis (plasmin -alpha2 plasmin inhibitor complex concentration is usually >4 microg/ml). Although several treatments were tried, DIC could not be controlled until the patient was given combined therapy of danaparoid (1,250 U/12 h, bolus IV) and tranexamic acid (0.5 g x 3/day, oral administration). This therapy may be beneficial when control for bleeding is required without restricting the ambulatory movement of patients by continuous drip.

Topics: Anticoagulants; Antifibrinolytic Agents; Aortic Aneurysm, Abdominal; Chondroitin Sulfates; Dermatan Sulfate; Disseminated Intravascular Coagulation; Drug Therapy, Combination; Heparitin Sulfate; Humans; Male; Middle Aged; Radiography; Tranexamic Acid

Glycosaminoglycans participate in several biological functions in the arterial wall through their specific structures. They undergo specific compositional and structural modifications during the development of vascular diseases. The present study was performed to determine the variations in the concentration and the structural characteristics of galactosaminoglycans--chondroitin sulfate (CS) and dermatan sulfate (DS)--during the progression of atherosclerosis and aneurysmal dilatation of the human abdominal aorta. The concentration of CS was increased 24% (p < or = 0.05) in atherosclerotic type II aortas, but it was significantly decreased (29%, p < or = 0.05) in atherosclerotic type V aortas and aneurysmal aortas (65%, p < or = 0.01). In contrast, the concentration of DS was almost constant in all stages of arterial disease examined. Significant structural alterations were detected in the disaccharide composition of galactosaminoglycans. The ratio of 6-sulfated to 4-sulfated disaccharides was increased in atherosclerotic type II aortas (4.0 instead of 3.1 in normal aortas) due to the marked increase of CS in this tissue. This ratio was significantly decreased in atherosclerotic type V and aneurysmal aortas (2.1 and 1.6, respectively) due to the significant reduction of CS in the respective tissues. In addition, significant decrease of the oversulfated disaccharides, which are mainly located in DS chains, was recorded in atherosclerotic and aneurysmal aortas. Particularly, deltadi-di(2,6)S were decreased 32% (p < or = 0.01) and 86% (p < or = 0.01) in atherosclerotic type II and V aortas and 88% (p < or = 0.01) in aneurysm. Deltadi-di(2,4)S were increased in atherosclerotic type II aortas (21%, p < or = 0.01), but significantly decreased in atherosclerotic type V (33%, p < or = 0.01) and aneurysmal aortas (56%, p < or = 0.01). The amounts of deltadi-di(4,6)S were not markedly affected in the diseased tissues. These results suggest that the concentration of galactosaminoglycans is differentially affected during the progression of atherosclerosis. Furthermore, the development of vascular disease is associated with specific structural modifications, especially with the significant reduction of particular types of oversulfated disaccharides, which may play essential biological roles in the arterial wall.

Topics: Adult; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Arteriosclerosis; Chemical Fractionation; Chondroitin ABC Lyase; Chondroitin Lyases; Chondroitin Sulfates; Dermatan Sulfate; Disaccharides; Electrophoresis, Capillary; Humans; Male; Middle Aged; Uronic Acids

Human abdominal aortic aneurysm (AAA) is a commonly occuring disease of blood vessels and is related to alterations in extracellular matrix molecules. In this study we report on the type and fine structural characterization of glycosaminoglycans (GAGs) present in AAA as compared with those present in normal abdominal aorta. Hyaluronan (HA), the galactosaminoglycans-chondroitin sulfate (CS) and dermatan sulfate (DS) with average molecular size (Mr) of 35-kDa-as well as heparan sulfate (HS) with Mr of 40-kDa were identified in both tissues. No significant intrabatch differences in total GAG content were identified in normal and aneurysmal aortas. Comparing, however, tissue composition and structure of GAGs between AAAs and normal aortas, significant differences (P < or = 0.001) were found. The overall GAG content in AAAs was approx. 60% lower than the normal ones. A 90% decrease in HS content, and 65 and 73% in CS and HA, respectively, were also recorded. In contrast, only a slight decrease in the amount of DS was noted (8%). Structural alterations in disaccharide composition of GAGs correspond mainly to significant decreases (P < or = 0.001) of HS-derived N-sulfated disaccharides, CS-derived 6-sulfated disaccharide and DS-derived disulfated disaccharides. These results demonstrate that the development of AAA is related to dramatic quantitative and structural modifications at the GAG level and this may well be attributed to the destruction of arterial wall architecture and further significant functional inadequacies of the tissue.

Topics: Aged; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Chondroitin Lyases; Chondroitin Sulfates; Chromatography, High Pressure Liquid; Dermatan Sulfate; Extracellular Matrix; Glycosaminoglycans; Humans; Hyaluronic Acid; Male; Middle Aged; Polysaccharides; Uronic Acids

The walls of human abdominal aortas and atherosclerosis-induced aneurysms contain similar amounts of collagen. The quantitative ratio between collagens of various types of this protein does not differ significantly either, whereas solubility of the collagen in aneurysmal wall and its susceptibility to the action of EDTA are distinctly decreased. In contrast with collagen, the amount of elastin in aneurysms is significantly lower. Total amount of glycosaminoglycans slightly decreased as compared with that of normal tissue, but the ratio of particular compounds varies. The percentage of chondroitin sulphate is increased and that of heparan sulphate significantly decreased. The significance of these changes in pathogenesis of aneurysms is discussed.

Topics: Adult; Aged; Aging; Aortic Aneurysm, Abdominal; Arteriosclerosis; Case-Control Studies; Chondroitin Sulfates; Collagen; Elastin; Female; Glycosaminoglycans; Humans; Keratan Sulfate; Male; Middle Aged; Solubility