Is the Watanabe heritable hyperlipidemic rabbit a suitable experimental model for percutaneous transluminal coronary angioplasty in humans? A light microscopic, immunohistochemical and ultrastructural study

Department of Cardiovascular Pathology, University of Amsterdam, The Netherlands.

OBJECTIVES. This study was designed to assess an experimental model for the study of mechanisms that underlie restenosis after percutaneous transluminal coronary angioplasty. BACKGROUND. The Watanabe heritable hyperlipidemic (WHHL) rabbit lacks the receptor for low density lipoproteins, produces atherosclerotic lesions very similar to those in humans and, therefore, could serve as a suitable model. METHODS. Percutaneous transluminal angioplasty was performed on the left subclavian artery of 10 homozygous rabbits. The animals were killed at a few hours or 3, 7, 14 or 28 days after the procedure. The artery was fixed by perfusion, and the site of angioplasty was examined by both light and electron microscopy with the use of conventional and immunohistochemical staining techniques. RESULTS. Angioplasty had caused a flap-like or dissecting tear into the media. At day 3, cells within the preexisting media adjacent to the injury had the ultrastructural characteristics of synthetic smooth muscle cells. At day 7, spindle cells at the site of injury stained either negative or very weakly positive with a marker for actin; ultrastructurally, these cells had the synthetic phenotype. At day 14, the spindle cells showed a mix of contractile and synthetic phenotypes. The surface was partially covered by endothelial cells. At day 28, the dominant cell type was the contractile smooth muscle cell and the surface was completely covered by endothelial cells. CONCLUSIONS. Both the injury and the response to injury after percutaneous transluminal angioplasty were almost identical to that seen in humans after coronary angioplasty. Thus, the WHHL rabbit appears to be an appropriate experimental model for use in further studies.

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