The Watanabe Heritable Hyperlipidemic Rabbit Is a Suitable Experimental Model to Study Differences in Tissue Response Between Intimal and Medial Injury After Balloon Angioplasty

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Abstract
The study evaluates whether the Watanabe heritable hyperlipidemic (WHHL) rabbit is an adequate model to study mechanisms that underlie differences in tissue response after postangioplasty injury. Postangioplasty studies of human coronary arteries have revealed that healing and restenotic processes differ depending on whether the laceration is limited to the atherosclerotic plaque or whether injury extends into the media. Forty-five homozygous WHHL rabbits underwent percutaneous transluminal angioplasty of the left subclavian artery. The inflated arterial segment was studied histologically at 3, 7, 14, 28, and 56 days, using conventional and immunohistochemical techniques to identify macrophages, smooth muscle cell (SMC) phenotypes, and cell proliferation. Electron microscopy was done to study reendothelialization. There were marked differences in response between those segments with medial injury and those with injury limited to the atherosclerotic plaque tissues. The latter category shows a distinct retardation in redifferentiation of SMCs, confirming previous observations in human coronary arteries. In these segments, moreover, cell proliferation occurred mainly in macrophages and spindle cells. Medial injury showed a more florid fibrocellular response, as in human coronary arteries, with cell proliferation initially confined to areas with dedifferentiated SMCs in the preexistent media and, once neointimal tissue was formed, among spindle cells also. The similarities with the repair processes encountered in postangioplasty human coronary arteries suggest that the WHHL rabbit is an adequate model to study differences in the response related to different types of angioplasty injury.

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