keratan-sulfate and Arteriosclerosis

The skeletal and corneal keratan sulfate proteoglycans show a different metabolic and structural heterogeneity. The domain structure of the carbohydrate chain has been shown to be different in various animal species. There are two major types of skeletal keratan sulfate proteoglycans with and without fucose. The protein cores of the corneal chicken keratan sulfate proteoglycan (lumican) and those of another small keratan sulfate proteoglycan (fibromodulin) have been sequenced. Keratan sulfate oligosaccharides belong to the members of an antigen family of the poly-N-acetyllactosamine series. Monoclonal antibodies and immunoassay procedures for keratan sulfate proteoglycans have been prepared. In osteoarthritis, no significant specific increase of keratan sulfate has been found. Keratan sulfate is a functional substitute for chondroitin sulfate in O2-deficient tissues.

Topics: Animals; Arteriosclerosis; Base Sequence; Carbohydrate Conformation; Carbohydrate Sequence; Chondroitin Sulfate Proteoglycans; Collagen; Cornea; Corneal Dystrophies, Hereditary; Humans; Keratan Sulfate; Lumican; Lysosomes; Molecular Sequence Data

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

Proteoglycans were isolated from either grossly normal or atherosclerotic pigeon aortas after extraction with 4 M guanidine hydrochloride and purification by ion-exchange and size-exclusion chromatography. The small-size proteoglycans (Kav 0.4, on Sepharose CL-4B) from both normal and atherosclerotic tissue contained primarily a dermatan sulfate proteoglycan with an intact molecular size of 220-330 kd and a 45-kd core protein. In addition to the dermatan sulfate proteoglycan, the preparation contained a proteoglycan recognized by monoclonal antibody (MAb) 5-D-4, indicating the presence of sulfated poly-N-acetyllactosamine sequences common to corneal and cartilage keratan sulfate. Electrophoresis on sodium dodecyl sulfate-polyacrylamide gel revealed a polydisperse proteoglycan of 60-150 kd that was recognized by MAb 5-D-4. Significantly greater immunoreactivity with MAb 5-D-4 was observed for atherosclerotic compared with normal artery. After endo-beta-D-galactosidase treatment of the proteoglycan from atherosclerotic aorta, diminished MAb 5-D-4 reactivity observed by both Western blot analysis and enzyme-linked immunosorbent assay demonstrated that the material was keratan sulfate. Endo-beta-D-galactosidase treatment of the intact proteoglycan generated core proteins of 28 and 38 kd. These studies suggest the presence of one or more keratan sulfate proteoglycans in grossly normal and atherosclerotic arteries. Immunochemical data suggest that sulfation of the keratan sulfate proteoglycan may be greater in atherosclerotic aorta.

Topics: Amidohydrolases; Animals; Antibodies, Monoclonal; Aorta; Arteriosclerosis; beta-Galactosidase; Blotting, Western; Chondroitin Lyases; Chondroitin Sulfate Proteoglycans; Columbidae; Dermatan Sulfate; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Glycoside Hydrolases; Keratan Sulfate; Lumican; Molecular Weight; Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase