Adipophilin expression is increased in symptomatic carotid atherosclerosis: correlation with red blood cells and cholesterol crystals.
OBJECTIVE
Adipophilin is an adipose differentiation-related protein expressed in lipid-containing cells. Using DNA microarray analysis, we previously found the adipophilin gene (ADFP) to be overexpressed in symptomatic carotid plaques (CP). This led us to further examine the role of adipophilin in carotid atherosclerosis relative to symptom status.


METHODS
Ninety-eight high-grade (>70%) CPs were obtained in carotid endarterectomy. The relative expression of ADFP mRNA was measured by quantitative real-time RT-PCR, and the relative amount of adipophilin protein was quantified with Western blotting. Detailed topographical correlations with extravasated red blood cells and extracellular cholesterol crystals were obtained by means of immunohistochemistry.


RESULTS
The relative expression of ADFP mRNA was increased in symptomatic compared with asymptomatic CPs at both the mRNA level (1.82+/-0.19[SE] versus 1.25+/-0.15, P=0.012) and the protein level (1.04+/-0.23 versus 0.46+/-0.14, P=0.043). Adipophilin colocalized with macrophage foam cells, extravasated red blood cells (P<0.0001), and cholesterol crystals (P<0.0001), and its expression associated with macroscopic ulceration of CP (P<0.0001).


CONCLUSIONS
Intraplaque hemorrhages may contribute to intracellular lipid accumulation and consequent adipophilin expression. Because adipophilin blocks cholesterol efflux from lipid-laden cells, they may die and develop a necrotic lipid core, thereby destabilizing the plaque.
Nuotio
Krista
K
Neuroscience Program, Biomedicum Helsinki, Haartmaninkatu, Helsinki, Finland. Krista.Nuotio@helsinki.fi
Isoviita
Pia M
PM
Saksi
Jani
J
Ijäs
Petra
P
Pitkäniemi
Janne
J
Sonninen
Riitta
R
Soinne
Lauri
L
Saimanen
Eija
E
Salonen
Oili
O
Kovanen
Petri T
PT
Kaste
Markku
M
Lindsberg
Perttu J
PJ
D000368:Aged; D002340:Carotid Artery Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002343:Carotid Artery, Internal / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism*; D003460:Crystallization; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009336:Necrosis; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D000070780:Perilipin-2
D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D010455:Peptides; D000070780:Perilipin-2; D002784:Cholesterol