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      Effects of Diabetes and Insulin Treatment of Diabetic Rats on Hyaluronan and Hyaluronectin Production in Injured Aorta

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          Abstract

          The present study was conducted to determine the effect of diabetes with and without insulin treatment on the production of hyaluronen (HA) and distribution of hyaluronectin (HN) in the rat aorta 14 days after injury with a catheter balloon. Injury increased intima-media wet weight (+11%) and DNA content (+37.5%). This increase was slightly enhanced in untreated diabetic rats (+14.7% for wet weight and +48.9% for DNA content) and was significantly greater in diabetic rats treated with insulin (+28.9% for wet weight and +54% for DNA content). HA content increase in the injured aorta of nondiabetic rats (+43.6%) was similar in untreated diabetic (+44.7%) and more pronounced in diabetic rats treated with insulin (+91.3%). HA was markedly expressed in the neointima of nondiabetic rats, particularly near the lumen of the aorta. In untreated diabetic rats, HA was present throughout the neointima and not mainly close to the lumen. HA staining in the neointima of diabetic rats treated with insulin was similar to that in nondiabetic rats. HN was strongly expressed throughout the neointima of all groups. Injury enhanced the production of a high molecular mass HN (>400 kDa); this was not observed either in untreated or in insulin-treated diabetic rats. In conclusion, insulin treatment promoted the proliferative response of aorta to injury and this was associated mainly with increased HA production. This finding suggests that HA, which has been shown to play a crucial role in smooth muscle cell proliferation and migration, may be involved in the promoting effect of insulin treatment on arterial wall reaction to injury.

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          Most cited references5

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          Identification of the proteoglycan versican in aorta and smooth muscle cells by DNA sequence analysis, in situ hybridization and immunohistochemistry.

          Versican is a large chondroitin sulfate proteoglycan (CSPG) initially identified in cultured human fibroblasts. Previous studies have shown that there is a versican-like molecule in cultured monkey smooth muscle cells. In this study, we have cloned and sequenced the large CSPG from cultured monkey smooth muscle cells, fetal and juvenile monkey aorta, and human fetal aorta. The cDNA sequence from human fetal aorta is completely homologous to the human fibroblast versican. We obtained 2.5 kb of cDNA sequence from monkey aortic RNA and cultured monkey smooth muscle cell RNA. This sequence covers three distinct domains of versican (hyaluronic acid binding domain, glycosaminoglycan attachment domain and protein binding domain) and demonstrates over 90% homology to the human versican sequence. In situ hybridization histochemistry indicates that the versican RNA transcript is located in the epithelium throughout the tunica media of the aorta. Western blot analysis and immunohistochemistry also confirm the presence of versican in human and monkey aorta.
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            Deposition of PG-M/versican is a major cause of human coronary restenosis after percutaneous transluminal coronary angioplasty.

            To clarify the mechanisms of restenosis, restenotic human tissue specimens obtained by directional coronary atherectomy (DCA) in 43 patients were immunohistochemically analysed for cell proliferation and deposition of PG-M/versican, an important extracellular matrix proteoglycan of the vessel wall. The patients were classified into five groups according to the period after percutaneous transluminal coronary angioplasty (PTCA): 0-1 month (N = 6), 1-3 months (N = 12), 3-6 months (N = 11), more than 6 months (N = 6) and de novo lesions (N = 8). The tissue specimens were of 35 restenotic lesions following PTCA and eight primary stenotic lesions with no prior PTCA. Total cell numbers in the atherectomy specimens increased significantly up to 3 months after PTCA. Most cells were alpha-smooth muscle actin (alpha-SMA)-positive. To evaluate cell proliferation, the specimens were immunostained for Ki-67 antigen (clone MIB-1). A significant increase in the positive ratio was observed up to 1 month after PTCA, although the labelling index was less than 1 per cent at every stage. The deposition of PG-M/versican, as analysed by immunohistochemistry, was greatest during the period 1-3 months after primary angioplasty, when restenosis detected by angiography progresses most actively. These results suggest that the peak of cell proliferation in the neointima occurs earlier than angiographic restenosis and that the deposition of PG-M/versican may be a major factor in restenosis following angioplasty.
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              Characterization of a hyaluronic acid-binding protein from sheep brain comparison with human brain hyaluronectin

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                Author and article information

                Journal
                JVR
                J Vasc Res
                10.1159/issn.1018-1172
                Journal of Vascular Research
                S. Karger AG
                1018-1172
                1423-0135
                1999
                June 1999
                18 June 1999
                : 36
                : 3
                : 209-221
                Affiliations
                aLaboratoire DIFEMA-MERCI, Faculté de Médecine-Pharmacie, bDépartement de Médecine Interne, CHU Rouen-Bois-Guillaume, cLaboratoire d’oncologie moléculaire et dLaboratoire de biochimie, Centre Henri Becquerel, Rouen, France
                Article
                25644 J Vasc Res 1999;36:209–221
                10.1159/000025644
                10393507
                33634f10-d926-498e-9a8e-b7c433fb3788
                © 1999 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Page count
                Figures: 4, Tables: 3, References: 36, Pages: 13
                Categories
                Research Paper

                General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
                Diabetes,Aorta,Insulin,Hyaluronan,Hyaluronectin,Injury

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