Decreased biglycan expression and differential decorin localization in human abdominal aortic aneurysms.
The hallmark feature of abdominal aortic aneurysm (AAA) is the progressive degeneration of aortic wall. Matrix proteoglycans (PGs) play important roles in the development of vascular diseases and the function of the tissue. In this study, we examined the concentration, expression and localization of the small extracellular matrix PG biglycan and decorin. The concentration of small PGs present in normal and aneurysmal aortas was determined by biochemical methods following extraction of the tissues with guanidine hydrochloride and treatment with collagenase/elastase, isolation by ion-exchange and gel chromatographies and identification by Western blotting. The levels of mRNA encoding for biglycan and decorin were evaluated in corresponding tissue samples by reverse transcriptase polymerase chain reaction (RT-PCR). Distribution of extracellular matrix macromolecules was examined using Movat's pentachrome staining and localization of biglycan and decorin by immunohistochemistry. Both normal and aneurysmal aortas contained almost equal amounts of decorin (1.13+/-0.08 and 1.22+/-0.10 mg uronic acid per g of dry defatted (dd) tissue, respectively). Furthermore, the expression of decorin was almost constant in both tissues. In normal specimens decorin accounts for 22% of total PGs, whereas in AAA ones for 60%, due to the significant loss of other matrix PGs. In contrast, the concentration of biglycan was markedly decreased in aneurysmal aortas (57%, 0.478+/-0.04 mg uronic acid per g of dd tissue) in comparison to normal ones (1.12+/-0.10 mg uronic acid per g of dd tissue). Biglycan accounts for 22% of total PGs in normal aortas and 25% of total in aneurysmal tissue. A similar decrease (60%) in the amounts of mRNA encoding for biglycan was observed in the AAA. Immunohistochemical study showed that all aortic layers of AAA were characterized by a significant loss of elastin, biglycan and other PGs/GAGs and replacement of these molecules with collagen fibrils and decorin. The obtained data suggest that the altered matrix architecture of aorta, i.e. the differential expression of biglycan and localization of decorin may well be crucial parameters accounting for the functional degeneration of the tissue and the development of aneurysmal dilatation.
Theocharis
Achilleas D
AD
Section of Organic Chemistry, Biochemistry and Natural Products, Department of Chemistry, Laboratory of Biochemistry, University of Patras, 261 10, Patras, Greece.
Karamanos
Nikos K
NK
D000368:Aged; D001012:Aorta, Abdominal / Q000378:metabolism*; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics / Q000378:metabolism*; D058578:Biglycan; D058575:Decorin; D016326:Extracellular Matrix Proteins; D006801:Humans; D008297:Male; D008875:Middle Aged; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C546884:BGN protein, human; D058578:Biglycan; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D012333:RNA, Messenger