Atheroprotective remodelling of vascular dermatan sulphate proteoglycans in response to hypercholesterolaemia in a rat model
Proteoglycan accumulation within the arterial intima has been implicated in atherosclerosis progression in humans. Nevertheless, hypercholesterolaemia is unable to induce intimal thickening and atheroma plaque development in rats. The study was performed to analyse proteoglycans modifications in rat...
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todo:paper_09599673_v95_n3_p181_Oberkersch2023-10-03T15:53:21Z Atheroprotective remodelling of vascular dermatan sulphate proteoglycans in response to hypercholesterolaemia in a rat model Oberkersch, R. Maccari, F. Bravo, A.I. Volpi, N. Gazzaniga, S. Calabrese, G.C. Aortic cells Atherosclerosis Dermatan sulphate proteoglycans Extracellular matrix beta actin biglycan chondroitin 6 sulfate chondroitin sulfate decorin dermatan sulfate galactosaminoglycan heparan sulfate high density lipoprotein cholesterol messenger RNA perlecan triacylglycerol tumor necrosis factor alpha versican animal experiment animal tissue aorta article atherosclerosis blood vessel wall cholesterol blood level cholesterol diet controlled study high performance liquid chromatography hypercholesterolemia immunochemistry male neointima nonhuman priority journal protein expression rat reverse transcription polymerase chain reaction smooth muscle fiber Western blotting aortic cells atherosclerosis dermatan sulphate proteoglycans extracellular matrix Animals Aorta Atherosclerosis Cholesterol Chondroitin Sulfate Proteoglycans Dermatan Sulfate Diet, Atherogenic Disease Models, Animal Extracellular Matrix Gene Expression Regulation Glycosaminoglycans Goats Humans Hypercholesterolemia Lipids Male Plaque, Atherosclerotic Rabbits Rats Rats, Wistar Tumor Necrosis Factor-alpha Proteoglycan accumulation within the arterial intima has been implicated in atherosclerosis progression in humans. Nevertheless, hypercholesterolaemia is unable to induce intimal thickening and atheroma plaque development in rats. The study was performed to analyse proteoglycans modifications in rats fed with a high-cholesterol diet to understand whether vascular wall remodelling protects against lesions. Sections obtained from rat aortas showed normal features, in intimal-to-media ratio and lipid accumulation. However, focal endothelial hyperplasia and neo-intima rearrangement were observed in high-cholesterol animals. Besides, hypercholesterolaemia induced an inflammatory microenviroment. We determined the expression of different proteoglycans from aortic cells by Western blot and observed a diminished production of decorin and biglycan in high-cholesterol animals compared with control (P < 0.01 and P < 0.05, respectively). Versican was increased in high-cholesterol animals (P < 0.05), whereas perlecan production showed no differences. No modification of the total content of glycosaminoglycans (GAGs) was found between the two experimental groups. In contrast, the chondroitin sulphate/dermatan sulphate ratio was increased in the high-cholesterol group as compared to the control (0.56 and 0.34, respectively). Structural alterations in the disaccharide composition of galactosaminoglycans were also detected by HPLC, as the ratio of 6-sulphate to 4-sulphate disaccharides was increased in high-cholesterol animals (P < 0.05). Our results suggest that attenuation of decorin and biglycan expression might be an effective strategy to inhibit the first step in atherogenesis, although specific GAG structural modification associated with the development of vascular disease took place. Results emphasize the potential application of therapies based on vascular matrix remodelling to treat atherosclerosis. © 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology. Fil:Gazzaniga, S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_09599673_v95_n3_p181_Oberkersch |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Aortic cells Atherosclerosis Dermatan sulphate proteoglycans Extracellular matrix beta actin biglycan chondroitin 6 sulfate chondroitin sulfate decorin dermatan sulfate galactosaminoglycan heparan sulfate high density lipoprotein cholesterol messenger RNA perlecan triacylglycerol tumor necrosis factor alpha versican animal experiment animal tissue aorta article atherosclerosis blood vessel wall cholesterol blood level cholesterol diet controlled study high performance liquid chromatography hypercholesterolemia immunochemistry male neointima nonhuman priority journal protein expression rat reverse transcription polymerase chain reaction smooth muscle fiber Western blotting aortic cells atherosclerosis dermatan sulphate proteoglycans extracellular matrix Animals Aorta Atherosclerosis Cholesterol Chondroitin Sulfate Proteoglycans Dermatan Sulfate Diet, Atherogenic Disease Models, Animal Extracellular Matrix Gene Expression Regulation Glycosaminoglycans Goats Humans Hypercholesterolemia Lipids Male Plaque, Atherosclerotic Rabbits Rats Rats, Wistar Tumor Necrosis Factor-alpha |
| spellingShingle |
Aortic cells Atherosclerosis Dermatan sulphate proteoglycans Extracellular matrix beta actin biglycan chondroitin 6 sulfate chondroitin sulfate decorin dermatan sulfate galactosaminoglycan heparan sulfate high density lipoprotein cholesterol messenger RNA perlecan triacylglycerol tumor necrosis factor alpha versican animal experiment animal tissue aorta article atherosclerosis blood vessel wall cholesterol blood level cholesterol diet controlled study high performance liquid chromatography hypercholesterolemia immunochemistry male neointima nonhuman priority journal protein expression rat reverse transcription polymerase chain reaction smooth muscle fiber Western blotting aortic cells atherosclerosis dermatan sulphate proteoglycans extracellular matrix Animals Aorta Atherosclerosis Cholesterol Chondroitin Sulfate Proteoglycans Dermatan Sulfate Diet, Atherogenic Disease Models, Animal Extracellular Matrix Gene Expression Regulation Glycosaminoglycans Goats Humans Hypercholesterolemia Lipids Male Plaque, Atherosclerotic Rabbits Rats Rats, Wistar Tumor Necrosis Factor-alpha Oberkersch, R. Maccari, F. Bravo, A.I. Volpi, N. Gazzaniga, S. Calabrese, G.C. Atheroprotective remodelling of vascular dermatan sulphate proteoglycans in response to hypercholesterolaemia in a rat model |
| topic_facet |
Aortic cells Atherosclerosis Dermatan sulphate proteoglycans Extracellular matrix beta actin biglycan chondroitin 6 sulfate chondroitin sulfate decorin dermatan sulfate galactosaminoglycan heparan sulfate high density lipoprotein cholesterol messenger RNA perlecan triacylglycerol tumor necrosis factor alpha versican animal experiment animal tissue aorta article atherosclerosis blood vessel wall cholesterol blood level cholesterol diet controlled study high performance liquid chromatography hypercholesterolemia immunochemistry male neointima nonhuman priority journal protein expression rat reverse transcription polymerase chain reaction smooth muscle fiber Western blotting aortic cells atherosclerosis dermatan sulphate proteoglycans extracellular matrix Animals Aorta Atherosclerosis Cholesterol Chondroitin Sulfate Proteoglycans Dermatan Sulfate Diet, Atherogenic Disease Models, Animal Extracellular Matrix Gene Expression Regulation Glycosaminoglycans Goats Humans Hypercholesterolemia Lipids Male Plaque, Atherosclerotic Rabbits Rats Rats, Wistar Tumor Necrosis Factor-alpha |
| description |
Proteoglycan accumulation within the arterial intima has been implicated in atherosclerosis progression in humans. Nevertheless, hypercholesterolaemia is unable to induce intimal thickening and atheroma plaque development in rats. The study was performed to analyse proteoglycans modifications in rats fed with a high-cholesterol diet to understand whether vascular wall remodelling protects against lesions. Sections obtained from rat aortas showed normal features, in intimal-to-media ratio and lipid accumulation. However, focal endothelial hyperplasia and neo-intima rearrangement were observed in high-cholesterol animals. Besides, hypercholesterolaemia induced an inflammatory microenviroment. We determined the expression of different proteoglycans from aortic cells by Western blot and observed a diminished production of decorin and biglycan in high-cholesterol animals compared with control (P < 0.01 and P < 0.05, respectively). Versican was increased in high-cholesterol animals (P < 0.05), whereas perlecan production showed no differences. No modification of the total content of glycosaminoglycans (GAGs) was found between the two experimental groups. In contrast, the chondroitin sulphate/dermatan sulphate ratio was increased in the high-cholesterol group as compared to the control (0.56 and 0.34, respectively). Structural alterations in the disaccharide composition of galactosaminoglycans were also detected by HPLC, as the ratio of 6-sulphate to 4-sulphate disaccharides was increased in high-cholesterol animals (P < 0.05). Our results suggest that attenuation of decorin and biglycan expression might be an effective strategy to inhibit the first step in atherogenesis, although specific GAG structural modification associated with the development of vascular disease took place. Results emphasize the potential application of therapies based on vascular matrix remodelling to treat atherosclerosis. © 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology. |
| format |
JOUR |
| author |
Oberkersch, R. Maccari, F. Bravo, A.I. Volpi, N. Gazzaniga, S. Calabrese, G.C. |
| author_facet |
Oberkersch, R. Maccari, F. Bravo, A.I. Volpi, N. Gazzaniga, S. Calabrese, G.C. |
| author_sort |
Oberkersch, R. |
| title |
Atheroprotective remodelling of vascular dermatan sulphate proteoglycans in response to hypercholesterolaemia in a rat model |
| title_short |
Atheroprotective remodelling of vascular dermatan sulphate proteoglycans in response to hypercholesterolaemia in a rat model |
| title_full |
Atheroprotective remodelling of vascular dermatan sulphate proteoglycans in response to hypercholesterolaemia in a rat model |
| title_fullStr |
Atheroprotective remodelling of vascular dermatan sulphate proteoglycans in response to hypercholesterolaemia in a rat model |
| title_full_unstemmed |
Atheroprotective remodelling of vascular dermatan sulphate proteoglycans in response to hypercholesterolaemia in a rat model |
| title_sort |
atheroprotective remodelling of vascular dermatan sulphate proteoglycans in response to hypercholesterolaemia in a rat model |
| url |
http://hdl.handle.net/20.500.12110/paper_09599673_v95_n3_p181_Oberkersch |
| work_keys_str_mv |
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