An imbalance between CD36 and ABCA1 protein expression favors lipid accumulation in stroke-prone ulcerated carotid plaques.
BACKGROUND
CD36 is a macrophage scavenger receptor mediating the uptake of modified lipoproteins, whereas the ABCA1 transporter counteracts this effect by mediating cellular lipid efflux. Based on a DNA microarray, we previously found that the CD36 and ABCA1 genes were overexpressed in symptom-causing carotid plaques (CP) compared with nonsymptom-causing CP. To evaluate their role in CP destabilization, we conducted detailed immunohistochemical studies on the localization of lipids, CD36 and ABCA1 proteins, extravasated red blood cells, and atheromatous/necrotic tissue.


METHODS
Ninety-two high-grade (>70%) stenosing CP obtained from carotid endarterectomy were Oil-red-O-stained for evaluation of neutral lipids. Subgroups of nonsymptom-causing and symptom-causing CP (n=42) were further analyzed by immunostaining adjacent histological sections against CD36 and ABCA1 and examining them microscopically.


RESULTS
When compared with nonsymptom-causing CP, the amount of extracellular lipid and the expression of CD36 protein were elevated in symptom-causing CP, but no difference was found in ABCA1 expression. These observations were also confirmed when ulcerated and nonulcerated CP were compared. In ulcerated CP, CD36 protein expression was higher than that of ABCA1, and the opposite was true in nonulcerated CP. CD36 colocalized with extravasated red blood cells and atheromatous or necrotic areas in the various types of CP.


CONCLUSIONS
Our results suggest that an imbalance between lipid influx (CD36) and efflux (ABCA1) favors lipid accumulation in macrophages of ulcerated CP, thus contributing to plaque destabilization. Furthermore, colocalization of CD36 protein with red blood cells suggests that intraplaque hemorrhages may contribute to the lipid load and thus the stability of CP.
Isoviita
Pia M
PM
Research Program of Molecular Neurology, Biomedicum Helsinki, Helsinki, Finland. pia.isoviita@helsinki.fi
Nuotio
Krista
K
Saksi
Jani
J
Turunen
Riitta
R
Ijäs
Petra
P
Pitkäniemi
Janne
J
Soinne
Lauri
L
Kaste
Markku
M
Kovanen
Petri T
PT
Lindsberg
Perttu J
PJ
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000097:blood*; D000368:Aged; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D018955:CD36 Antigens / Q000032:analysis / Q000097:blood*; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016893:Carotid Stenosis / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D004912:Erythrocytes / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D050356:Lipid Metabolism / Q000502:physiology*; D052439:Lipid Metabolism Disorders / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology*; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015854:Up-Regulation / Q000502:physiology
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D015415:Biomarkers; D018955:CD36 Antigens