Relationship of arterial wall uptake of radiolabeled liposomes to the presence of monocyte/macrophage cells in the hypertensive and atherosclerotic arterial wall.
In vivo radiolabeled liposome uptake in 5 sham-operated, 7 coarctation-induced hypertensive, and 8 atherosclerotic arterial walls from New Zealand White rabbits was compared to determine the mechanism of arterial wall uptake of liposomes. Uptake between the three groups was significantly different (P less than 0.001) with a 3-fold difference in uptake between the sham-operated and hypertensive groups and the hypertensive and atherosclerotic groups. Liposome uptake was significantly higher in the atherosclerotic group of animals (P less than 0.05). Avidin-biotin immunoperoxidase staining for monocyte/macrophage cells revealed that liposome uptake increased concomitantly with arterial wall monocyte/macrophage cellular invasion and that liposome localization, determined by autoradiography, paralleled the monocyte/macrophage cellular distribution in both hypertensive and atherosclerotic arterial walls. This study provides the first direct evidence that liposomes can escape from the circulation and enter the diseased arterial wall. Furthermore, it suggests that one possible mechanism of arterial wall uptake of liposomes is via the monocyte/macrophage cell which avidly and preferentially engulfs liposomes and then passively carries them into the arterial wall during hypertensive and atherosclerotic lesion development. Liposomes could potentially be used to carry agents into the arterial wall in the study of arterial wall lesion development.
Hodis
H N
HN
Atherosclerosis Research Institute, University of Southern California School of Medicine, Los Angeles 90033.
Amartey
J K
JK
Crawford
D W
DW
Wickham
E
E
Sharma
R C
RC
Blankenhorn
D H
DH
D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001161:Arteriosclerosis / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D001345:Autoradiography; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008081:Liposomes / Q000493:pharmacokinetics*; D008264:Macrophages / Q000473:pathology / Q000502:physiology*; D008297:Male; D009000:Monocytes / Q000473:pathology / Q000502:physiology*; D011817:Rabbits
D008081:Liposomes; D002784:Cholesterol