Author:
Brasselet Camille,Durand Eric,Addad Faouzi,Zen Ayman Al Haj,Smeets Mirjam B.,Laurent-Maquin Dominique,Bouthors Sylvie,Bellon Georges,de Kleijn Dominique,Godeau Gaston,Garnotel Roselyne,Gogly Bruno,Lafont Antoine
Abstract
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 β-aminopropionitrile (β-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 β-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 β-APN-treated animals. The remodeling index was significantly higher in β-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 β-APN-treated animals: 32% (SD 16) vs. 48% (SD 24) ( P = 0.02). Neointimal collagen density was significantly lower in β-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.
Publisher
American Physiological Society
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology
Cited by
62 articles.
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