Collagen and elastin cross-linking: a mechanism of constrictive remodeling after arterial injury.
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 beta-aminopropionitrile (beta-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 beta-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 beta-APN-treated animals. The remodeling index was significantly higher in beta-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 beta-APN-treated animals: 32% (SD 16) vs. 48% (SD 24) (P = 0.02). Neointimal collagen density was significantly lower in beta-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.
Brasselet
Camille
C
INSERM E0016, Faculté de Médecine Paris V, Université René Descartes, France.
Durand
Eric
E
Addad
Faouzi
F
Al Haj Zen
Ayman
A
Smeets
Mirjam B
MB
Laurent-Maquin
Dominique
D
Bouthors
Sylvie
S
Bellon
Georges
G
de Kleijn
Dominique
D
Godeau
Gaston
G
Garnotel
Roselyne
R
Gogly
Bruno
B
Lafont
Antoine
A
D000629:Aminopropionitrile / Q000494:pharmacology; D000792:Angiography; D000818:Animals; D001158:Arteries / Q000293:injuries / Q000378:metabolism* / Q000473:pathology*; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D002404:Catheterization; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D023903:Coronary Restenosis / Q000378:metabolism / Q000473:pathology; D004549:Elastin / Q000737:chemistry / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D005263:Femoral Artery / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D046529:Microscopy, Electron, Transmission; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011817:Rabbits
D004791:Enzyme Inhibitors; D000629:Aminopropionitrile; D003094:Collagen; D004549:Elastin; D008249:Protein-Lysine 6-Oxidase