Compositional and structural alterations of chondroitin and dermatan sulfates during the progression of atherosclerosis and aneurysmal dilatation of the human abdominal aorta.
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.
Theocharis
Achilleas D
AD
Laboratory of Biochemistry, Section of Organic Chemistry, Biochemistry and Natural Products, Department of Chemistry, University of Patras, 26110 Patras, Greece.
Theocharis
Dimitrios A
DA
De Luca
Giancarlo
G
Hjerpe
Anders
A
Karamanos
Nikos K
NK
D000328:Adult; D001012:Aorta, Abdominal / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D017544:Aortic Aneurysm, Abdominal / Q000209:etiology / Q000378:metabolism*; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism*; D005591:Chemical Fractionation; D019765:Chondroitin ABC Lyase / Q000378:metabolism; D002808:Chondroitin Lyases / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000737:chemistry / Q000378:metabolism*; D003871:Dermatan Sulfate / Q000737:chemistry / Q000378:metabolism*; D004187:Disaccharides / Q000378:metabolism; D019075:Electrophoresis, Capillary / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D014574:Uronic Acids / Q000378:metabolism
D004187:Disaccharides; D014574:Uronic Acids; D003871:Dermatan Sulfate; D002809:Chondroitin Sulfates; D002808:Chondroitin Lyases; D019765:Chondroitin ABC Lyase