title: Cholesterol-dependent changes of glycosaminoglycan pattern in human aorta.
abstract: Glycosaminoglycans are regular constituents of the arterial wall and essential for its structure and function. The arteriosclerosis-dependent changes of glycosaminoglycans were investigated, the degree of arteriosclerosis was monitored by the cholesterol content of the tissue. Histological characterization was achieved by electron microscopy. Total glycosaminoglycans were isolated from 33 delipidated segments of human aorta thoracica after exhaustive proteolytic digestion, and fractionated into the individual glycosaminoglycans by a multistep purification procedure. Chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS), and hyaluronate (HA) were identified and quantified by chemical and enzymatic analysis. The concentration of total and individual glycosaminoglycans, expressed as mg/g delipidated dry weight of tissue, decreased significantly with increasing cholesterol content of tissue (p = 0.0005-0.005). The extent of decrease differed between the individual glycosaminoglycans as indicated by a shift in the CS/DS:HA:HS ratio from 47:32:21 in low cholesterol aortic segments to 59:29:12 in cholesterol-rich specimens. Determination of the relative molecular masses (Mr) revealed 58 kDa for CS/DS and 92 kDa for HS with a (statistically not significant) increase of the molecular mass of CS/DS and a decrease of HS with increasing cholesterol content. The copolymeric CS/DS glycosaminoglycans were disintegrated enzymatically into CS and DS containing fragments. A significantly higher relative DS content (p = 0.01) was found in cholesterol-rich arterial tissue (32.5%) as compared with low cholesterol tissue samples (28.8%). Cell culture experiments revealed that human arterial HS is able to inhibit the proliferation of cultured human arterial smooth muscle cells. The HS concentration required for a 30% inhibition of smooth muscle cell proliferation was in the same order as the tissue concentration of HS. This confirms the function of HS as an endogenous inhibitor of cell division and its impact for the development of atherosclerosis.
authors.affiliation: Institut für Humangenetik der Universität, Bonn, FRG.
authors.forename: R
authors.initials: R
authors.lastname: Kruse
authors.forename: M
authors.initials: M
authors.lastname: Merten
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.forename: A
authors.initials: A
authors.lastname: Schmidt
authors.forename: W
authors.initials: W
authors.lastname: Völker
authors.forename: E
authors.initials: E
authors.lastname: Buddecke
mesh_terms: D001013:Aorta, Thoracic / Q000737:chemistry* / Q000187:drug effects / Q000648:ultrastructure; D001161:Arteriosclerosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000032:analysis*; D002809:Chondroitin Sulfates / Q000032:analysis; D003871:Dermatan Sulfate / Q000032:analysis; D006025:Glycosaminoglycans / Q000032:analysis*; D006497:Heparan Sulfate / Q000494:pharmacology; D006801:Humans; D008854:Microscopy, Electron; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000737:chemistry* / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D002784:Cholesterol; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D006025:Glycosaminoglycans; D006497:Heparan Sulfate