© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
Increased collagen turnover is only partly associated with collagen fiber deposition in the arterial response to injury
aExperimental Cardiology Laboratory, University Medical Center, Utrecht, The Netherlands
bInteruniversity Cardiology Institute of the Netherlands (ICIN), Utrecht, The Netherlands
* Corresponding author. Experimental Cardiology Laboratory, University Medical Center, Heidelberglaan 100, Room G02-523, 3584 CX Utrecht, The Netherlands. Tel: +31-30-2507155; fax: +31-30-2522693. d.dekleijn{at}hli.azu.nl
Objective: In the arterial response to injury, collagen breakdown has been studied extensively, but little is known on collagen synthesis and fiber formation. Here, we studied in vivo collagen synthesis and collagen fiber content in relation to collagen breakdown following arterial balloon injury. Methods and results: Twenty-five New Zealand White rabbits were balloon dilated in femoral and iliac arteries and terminated at 2, 7, 14 and 28 days. From day 7, both constrictive arterial remodeling and intimal hyperplasia were observed. Collagen degradation, synthesis and fiber content were studied using zymography, quantitative Polymerase Chain Reaction, Western blotting and picrosirius red staining. Collagen synthesis, reflected by procollagen I and heat shock protein 47 (Hsp47) expression, increased at day 2 with a maximum at day 14 and was accompanied by increased collagen breakdown as reflected by matrix metalloproteinase-1 and -2 levels. Collagen content in media and adventitia only increased between days 2 and 7 after balloon injury. Conclusions: In the first week after arterial injury, increased collagen content is associated with increased collagen synthesis and degradation. However, after 1 week, collagen turnover remains high in contrast to increased collagen fiber content. This suggests that after 1 week, collagen turnover is used for other processes like cell migration and arterial remodeling.
KEYWORDS Angioplasty; Gene expression; Restenosis; Extracellular matrix; Matrix metalloproteinases
Time for primary review 23 days
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