The Biologic Behavior of Balloon Hyperinflation–Induced Arterial Lesions in Hypercholesterolemic Pigs Depends on the Presence of Foam Cells

Abstract

Abstract Lack of a large-animal model of accelerated atherosclerosis has limited study of the biologic behavior of atherosclerotic lesions. We hypothesized that mechanical vascular trauma combined with diet-induced hypercholesterolemia would result in rapid development of complex atherosclerosis-like lesions. Accordingly, we induced deep injury to a carotid artery by repetitive balloon hyperinflations in minipigs that were fed either an atherogenic diet (n=30) or a standard diet (controls, n=4) and examined the resultant lesions 1 month later. The neointimal lesions that evolved in 23 patent vessels from cholesterol-fed animals were complex, exhibiting infiltration of smooth muscle and foam cells and evidence of organized thrombus, recent thrombus, hemorrhage, and calcification. Lesions were separable histologically into two groups: foam-cell rich (n=12), with 33±10 foam cells per high-power field, and foam-cell poor (n=11), with 4±1 foam cells per high-power field. Minipigs with foam cell–rich lesions had higher serum cholesterol levels than those with foam cell–poor lesions (712±178 vs 468±240 mg/dL, P <.02). The incidence of intralesional thrombus was also significantly greater in foam cell–rich than in foam cell–poor lesions (50% vs 9%, P <.04). In addition, the degree of luminal stenosis was greater in the presence of lesions containing thrombus compared with those without thrombus (60±38% vs 30±29%, P =.05). Lesions in the control animals were fibrocellular and lacked foam cells and thrombus. Thus, hypercholesterolemia appeared to affect lesion composition and behavior. Lesions with an abundance of foam cells were more likely to show evidence of intralesional thrombosis, which was associated with increased luminal stenosis. Our findings suggest that foam cells may predispose to lesion instability and thrombosis, leading to even more severe luminal obstruction.