Arterial heparan sulfate proteoglycans inhibit vascular smooth muscle cell proliferation and phenotype change in vitro and neointimal formation in vivo

Bingley, J. A., Hayward, I. P., Campbell, J. H. and Campbell, G. R. (1998) Arterial heparan sulfate proteoglycans inhibit vascular smooth muscle cell proliferation and phenotype change in vitro and neointimal formation in vivo. Journal of Vascular Surgery, 28 2: 308-318.


Author Bingley, J. A.
Hayward, I. P.
Campbell, J. H.
Campbell, G. R.
Title Arterial heparan sulfate proteoglycans inhibit vascular smooth muscle cell proliferation and phenotype change in vitro and neointimal formation in vivo
Journal name Journal of Vascular Surgery   Check publisher's open access policy
ISSN 0741-5214
Publication date 1998
Sub-type Article (original research)
DOI 10.1016/S0741-5214(98)70167-3
Volume 28
Issue 2
Start page 308
End page 318
Total pages 11
Publisher Elsevier
Language eng
Abstract Purpose: The aim of this study was to determine whether heparan sulfate proteoglycans (HSPGs) from the normal arterial wall inhibit neointimal formation after injury in vivo and smooth muscle cell (SMC) phenotype change and proliferation in vitro. Methods: Arterial HSPGs were extracted from rabbit aortae and separated by anion-exchange chromatography. The effect of HSPGs, applied in a periadventitial gel, on neointimal formation was assessed 14 days after balloon catheter injury of rabbit carotid arteries. Their effect on SMC phenotype and proliferation was measured by point-counting morphometry of the cytoplasmic volume fraction of myofilaments (Vvmyo) and H-3-thymidine incorporation in SMCs in culture. Results: Arterial HSPGs (680 mu g) reduced neointimal formation by 35% at 14 days after injury (P =.029), whereas 2000 mu g of the low-molecular-weight heparin Enoxaparin was ineffective. HSPGs at 34 mu g/mL maintained subconfluent primary cultured SMCs with the same high Vvmyo (52.1% +/- 13.8%) after 5 days in culture as did cells freshly isolated from the arterial wall (52.1% +/- 15.1%). In contrast, 100 mu g/mL Enoxaparin was ineffective in preventing phenotypic change over this time period (Vvmyo 38.9% +/- 14.6%, controls 35.9% +/- 12.8%). HSPGs also inhibited 3H-thymidine incorporation into primary cultured SMCs with an ID50 value of 0.4 mu g/mL compared with a value of 14 mu g/ml; for Enoxaparin (P <.01). Conclusion: When used periadventitially in the rabbit arterial injury model, natural arterial HSPGs are effective inhibitors of neointimal formation. In vitro, the HSPGs maintain SMCs in a quiescent state by inhibiting phenotypic change and DNA synthesis. This study suggests that HSPGs may be a natural agent for the treatment of clinical restenosis.
Keyword Surgery
Peripheral Vascular Disease
Subendothelial Extracellular-matrix
Proteoheparan Sulfate
Endothelial Injury
Growth-factor
Restenosis
Angioplasty
Expression
Biology
Rabbit
Atherosclerosis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Australian Institute for Bioengineering and Nanotechnology Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 56 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 58 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Access Statistics: 63 Abstract Views  -  Detailed Statistics
Created: Mon, 13 Aug 2007, 10:34:26 EST