Rabbit plaque models closely resembling lesions in human coronary artery disease.
BACKGROUND
A suitable animal model is required to investigate plaque biology. Here, we examined 6 rabbit models of plaque generated by balloon injury and sequential combinations of normal and high-cholesterol diets.


RESULTS
Fifty-eight male Japanese White rabbits were used. Lipid-rich macrophages accumulated in the center of the intima, and smooth muscle cells were located on the luminal side of the intima (similar to stable plaques in human coronary arteries) of a model in which balloon injury was followed by a normal diet for 4 weeks and then by a high-cholesterol diet for 4 weeks. Extending the high-cholesterol diet for a further 4 weeks increased accumulation of lipid-rich macrophages, diminished the amounts of elastic fibers and smooth muscle cells in the intima and caused the expression of matrix metalloproteinase-9 and tissue factor. All of these features are characteristic of unstable plaques. Moreover, quantitative analysis revealed that matrix metalloproteinase-9 expression and elastic-fiber content inversely correlated with statistical significance (R(2) = 0.52, p = 0.0003).


CONCLUSIONS
A high-cholesterol diet for 0 to 8 weeks after a normal diet for the first 4 weeks following balloon injury induced various arterial lesions resembling the diffuse intimal thickening, as well as stable and unstable plaques that accumulate in human coronary arteries. The present models might be useful for plaque studies.
Okabe
Taichi
T
First Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Hoshiga
Masaaki
M
Negoro
Nobuyuki
N
Nakakoji
Takahiro
T
Arishiro
Kumiko
K
Ishihara
Tadashi
T
Ueno
Hikaru
H
Hanafusa
Toshiaki
T
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000818:Animals; D002455:Cell Division / Q000502:physiology; D002791:Cholesterol, Dietary / Q000494:pharmacology; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology*; D003331:Coronary Vessels / Q000293:injuries / Q000473:pathology*; D004195:Disease Models, Animal; D004548:Elasticity; D005487:Foam Cells / Q000473:pathology; D006801:Humans; D008055:Lipids / Q000097:blood; D008099:Liver / Q000201:enzymology; D008264:Macrophages / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D011817:Rabbits; D013925:Thromboplastin / Q000378:metabolism
D002791:Cholesterol, Dietary; D008055:Lipids; D013925:Thromboplastin; D020780:Matrix Metalloproteinase 9