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