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This Article Full Text Full Text (PDF) All Versions of this Article: 289/5/H2228    most recent 00410.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Brasselet, C. Articles by Lafont, A. Search for Related Content PubMed PubMed Citation Articles by Brasselet, C. Articles by Lafont, A.

Collagen and elastin cross-linking: a mechanism of constrictive remodeling after arterial injury

¹INSERM E0016, Faculté de Médecine Paris V, Université René Descartes, Paris; ²Department of Cardiology and ⁵Laboratoire Central de Biochimie, Hôpital Robert Debré, and ⁴INSERM ERM 0203 and IFR 53, Reims, France; and ³Experimental Cardiology Laboratory, University Medical Center, Utrecht, The Netherlands

Submitted 28 April 2005 ; accepted in final form 31 May 2005

Constrictive remodeling after arterial injury is related to collagen accumulation. Cross-linking has been shown to induce a scar process in cutaneous wound healing and is increased after arterial injury. We therefore evaluated the effect of cross-linking inhibition on qualitative and quantitative changes in collagen, elastin, and arterial remodeling after balloon injury in the atherosclerotic rabbit model. Atherosclerotic-like lesions were induced in femoral arteries of 28 New Zealand White rabbits by a combination of air desiccation and a high-cholesterol diet. After 1 mo, balloon angioplasty was performed in both femoral arteries. Fourteen rabbits were fed -aminopropionitrile (-APN, 100 mg/kg) and compared with 14 untreated animals. The remodeling index, i.e., the ratio of external elastic lamina at the lesion site to external elastic lamina at the reference site, was determined 4 wk after angioplasty for both groups. Pyridinoline was significantly decreased in arteries from -APN-treated animals compared with controls, confirming inhibition of collagen cross-linking: 0.30 (SD 0.03) and 0.52 (SD 0.02) mmol/mol hydroxyproline, respectively (P = 0.002). Scanning and transmission electron microscopy showed a profound disorganization of collagen fibers in arteries from -APN-treated animals. The remodeling index was significantly higher in -APN-treated than in control animals [1.1 (SD 0.3) vs. 0.8 (SD 0.3), P = 0.03], indicating favorable remodeling. Restenosis decreased by 33% in -APN-treated animals: 32% (SD 16) vs. 48% (SD 24) (P = 0.02). Neointimal collagen density was significantly lower in -APN-treated animals than in controls: 23.0% (SD 3.8) vs. 29.4% (SD 4.0) (P = 0.004). These findings suggest that collagen and elastin cross-linking plays a role in the healing process via constrictive remodeling and restenosis after balloon injury in the atherosclerotic rabbit model.

angioplasty; -aminopropionitrile

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