Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The composition and content of aortic glycosaminoglycans were studied in groups of rhesus monkeys fed control or atherogenic diets for 9 or 19 months. Aortic uronic acid content was significantly increased in both groups of monkeys with atherosclerosis. The major glycosaminoglycan in both control and atherosclerotic aortas was chondroitin sulfate with lesser amounts of heparan sulfate, dermatan sulfate, and hyaluronic acid. Dermatan sulfate was the only glycosaminoglycan to show a statistically significant elevation (65 to 87 per cent) in animals fed the atherogenic diet. This increase was positively correlated with the increased accumulation of aortic cholesterol (r = 0.4709, p less than 0.05). The results indicate that dermatan sulfate may be the major glycosaminoglycan involved during the early events of atherogenesis perhaps through retention of lipoprotein in the atherosclerotic artery.
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PMID:Aortic total glycosaminoglycan and dermatan sulfate changes in atherosclerotic rhesus monkeys. 10 Jun 55

The acidic glycosaminoglycans (AGAG) of the human coronary arterial tree (the main left and right branches and their distal portions) were analyzed by enzymatic methods employing chondroitinases, hyaluronidase and heparitinase. The AGAG content of human coronary arteries was highest in the left branch, intermediate in the right branch and lowest in the distal portions. Some compositional differences in AGAG were found in these three parts. The amount of AGAG in the coronary arterial tree decreased with increasing severity of atherosclerosis. The main AGAG were heparan sulfate (HS) and chondroitin 6-sulfate (C-6S), constituting 33-38% and 24-36% of the total AGAG, respectively. Dermatan sulfate (DS) and chondroitin 4-sulfate (C-4S) each comprised 1/5-1/10 of the total AGAG. Hyaluronic acid (HA) and oversulfated DS comprised smaller proportions of the total AGAG. A small amount of heparin was occasionally detected in the coronary arterial tree, particularly in the distal portions. The lipid content of the main branches was increased in mildly atherosclerotic parts but diminished in severely affected parts. The water content was relatively higher in the main branches and decreased with severity of atherosclerosis. A possible function of these AGAG in atherosclerosis is discussed with respect to the compositional changes.
Atherosclerosis 1982 Oct
PMID:Acidic glycosaminoglycan, lipid and water contents in human coronary arterial branches. 715 90

Glycosaminoglycan composition of normal saphenous veins and atherosclerotic saphenous vein grafts is reported. Dermatan sulfate is the main glycosaminoglycan present in both normal saphenous veins and saphenous vein grafts. These tissues also contain chondroitin sulfate and heparan sulfate. Although the total amount of glycosaminoglycans decreased in the grafts (compared with normal saphenous veins), the grafts showed an increase in the relative amounts of dermatan sulfate and chondroitin sulfate. Heparan sulfate was decreased, compared with normal controls. These findings suggest the involvement of blood vessel glycosaminoglycans (not only the arterial glycosaminoglycans) in the process of atherosclerosis.
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PMID:Glycosaminoglycan distribution in atherosclerotic saphenous vein grafts. 772 4

Dermatan sulfate proteoglycans (DSPG) were extracted from intima-media of grossly normal aortic tissue of White Carneau pigeons and were purified by ion exchange chromatography on DEAE-Sephacel followed by size exclusion chromatography on Sepharose CL-4B. The major aortic DSPG had an average size of 310 kDa. The core protein resulting from treatment of the PG with chondroitinase ABC: (1) was found to be approximately 48 kDa by SDS-polyacrylamide gel electrophoresis; (2) was recognized by monoclonal antibody (Mab) 2-B-6 but not by Mab 3-B-3 on Western blots, indicating the presence of delta Di-4S and absence of delta Di-6S; (3) was glycosylated with Asn-linked oligosaccharides; (4) contained a high content of Asx, Glx and Leu, similar to that found for core proteins of this size from other tissues and species and (5) contained an N-terminal sequence (Asp-Glu-Gly-Xaa-Ala-Asp-Met-Pro-Pro-Xaa-Asp-Asp-Pro-Val- Ile-(ile)-Gly-Phe-), which was similar to sequences of DSPG core proteins previously described as 'decorin' and distinct from DSPG described as 'biglycan'. The results suggest that the major DSPG of aorta can be classified as a decorin molecule. The overall size of the DSPG in aorta was larger than decorin molecules described in non-arterial tissues of other species. Evidence is presented to conclude the larger size results from more than one dermatan sulfate-glycosaminoglycan chain.
Atherosclerosis 1993 Jan 04
PMID:Structural properties and partial protein sequence analysis of the major dermatan sulfate proteoglycan of pigeon aorta. 845 55

Glycosaminoglycans (GAGs) bound to various proteoglycans (PGs) present in the cardiovascular system have been proposed to perform a wide range of functions. These include conferring viscoelastic properties; interacting with and modulating growth factors and enzymes; and as receptors and co-receptors in lipoprotein metabolism. Binding of apoB-100 lipoproteins, particularly low density lipoproteins (LDL), to GAGs of extracellular matrix PGs in arteries has been proposed to be an initiating event in development of atherosclerosis. This study was initiated with the aim of getting an overview of the binding patterns of different lipoprotein subclasses with individual GAG categories. We thus evaluated the interaction of lipoproteins with GAGs commonly found in the cardiovascular system using a gel mobility-shift assay developed for this purpose. The same procedure was used to measure lipoproteins binding to metabolically [(35)S]-labeled whole PGs prepared from three cell types, arterial smooth muscle cells, THP-1 macrophages and from HepG2 cells. The effect of GAG composition on PGs on lipoprotein binding was evaluated by enzymatic degradation of the carbohydrate chains. Heparan sulfate was found to bind beta very low density lipoproteins (beta-VLDL) and a chylomicron remnant model (beta-VLDL+apoE), but not LDL. Dermatan sulfate was found to bind LDL, but not beta-VLDL or the chylomicron remnant model. Chondroitin sulfate and heparin were found to bind all lipoproteins tested (LDL, beta-VLDL and beta-VLDL+apoE) although with different affinities. We can conclude that each lipoprotein subclass tested binds a specific assortment of the GAGs tested. The observations made contribute to the understanding of new and complex mechanisms by which carbohydrate and lipid metabolism may be linked.
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PMID:Glycosaminoglycan-lipoprotein interaction. 1244 68

Heparin cofactor II (HCII) is a serine protease inhibitor (serpin) found in high concentrations in human plasma. Despite its discovery >30 years ago, its physiological function is still poorly understood. It is known to inhibit thrombin, the predominant coagulation protease, and HCII-thrombin complexes have been found in plasma, yet it is thought to contribute little to normal hemostasis. However, thrombin has several other physiological functions, and therefore many biological roles for HCII need consideration. The unique structure and mechanism of action of HCII have helped guide our understanding of HCII. In particular, HCII binds many glycosaminoglycans (GAGs) such as heparin and heparin sulfate as well as several different polyanions to enhance its inhibition of thrombin. Distinctly, HCII is able to use the GAG dermatan sulfate for accelerated thrombin inhibition. Dermatan sulfate is found in high concentrations in the walls of blood vessels as well as in placental tissue. This knowledge has led to research indicating that HCII may play a protective role in atherosclerosis and placental thrombosis. Additionally, pharmaceuticals are being developed that use the dermatan sulfate activation of HCII for anticoagulation. Although much research is still needed to fully understand HCII, this humble protein may have significant impact in our medical future. This article reviews the laboratory history, protein characteristics, structure-activity relationships, protease inhibition, physiological function, and medical relevance of HCII in hopes of regenerating interest in this sometimes forgotten serpin.
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PMID:Heparin cofactor II: discovery, properties, and role in controlling vascular homeostasis. 2180 39