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

Lena Yao, Catherine C. Moody, Elke Schönherr … (1994)

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.

T Yoshida, Ryohei Nakano, N Isaka … (1996)

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

Bertrand Delpech, Catherine Maingonnat, Annie Delpech … (1991)

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Journal

Journal ID (publisher-id): JVR

Journal ID (nlm-ta): J Vasc Res

Journal ID (doi): 10.1159/issn.1018-1172

Title: Journal of Vascular Research

Publisher: S. Karger AG

ISSN (Print): 1018-1172

ISSN (Electronic): 1423-0135

Publication date Subscription-year: 1999

Publication date (Print): June 1999

Publication date (Electronic): 18 June 1999

Volume: 36

Issue: 3

Pages: 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

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Publisher ID: 25644 Other ID: J Vasc Res 1999;36:209–221

DOI: 10.1159/000025644

PubMed ID: 10393507

SO-VID: 33634f10-d926-498e-9a8e-b7c433fb3788

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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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Karger: Cardiovascular System

Most cited references 5

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

Deposition of PG-M/versican is a major cause of human coronary restenosis after percutaneous transluminal coronary angioplasty.

Characterization of a hyaluronic acid-binding protein from sheep brain comparison with human brain hyaluronectin

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