Radiolabeled Native Low-Density Lipoprotein Injected Into Patients With Carotid Stenosis Accumulates in Macrophages of Atherosclerotic Plaque

BACKGROUND: Accumulation of LDL within the arterial wall appears to play a crucial role in the initiation and progression of atherosclerotic plaque. The dynamic sequence of this event has not been fully elucidated in humans. METHODS AND RESULTS: In 7 patients with previous transient ischemic attack or stroke and critical (>70%) carotid stenosis, autologous native [(125)I]-labeled LDL or [(125)I]-labeled human serum albumin were injected 24 to 72 hours before endarterectomy. Carotid specimens obtained at endarterectomy were analyzed by autoradiography and immunohistochemistry. Autoradiographic study showed that LDL was localized prevalently in the foam cells of atherosclerotic plaques, whereas the accumulation in the lipid core was negligible. Immunohistochemistry revealed that foam cells that had accumulated radiolabeled LDL were mostly CD68 positive, whereas a small number were alpha-actin positive. No accumulation of the radiotracer was detected in atherosclerotic plaques after injection of radiolabeled human serum albumin. In 3 patients treated for 4 weeks with vitamin E (900 mg/d), an almost complete suppression of radiolabeled LDL uptake by macrophages was observed. CONCLUSIONS: This study shows that circulating LDL rapidly accumulates in human atherosclerotic plaque. The prevalent accumulation of LDL by macrophages provides strong support to the hypothesis that these cells play a crucial role in the pathogenesis of atherosclerosis.