Microarray analysis reveals overexpression of CD163 and HO-1 in symptomatic carotid plaques.
OBJECTIVE
We studied by microarray analysis whether symptomatic and asymptomatic carotid plaques from the same patient differ in gene expression and whether the same changes are present in an independent sample set.


RESULTS
Carotid plaques from four patients with bilateral high-grade stenosis, one being symptomatic and the other asymptomatic, were analyzed on Affymetrix U95Av2 arrays. 33 genes showed >1.5-fold change between symptomatic and asymptomatic plaques in an intraindividual comparison with FDR ranging from 0.28 to 0.40. Three genes involved in iron-heme homeostasis, CD163, HO-1, and transferrin receptor, were further analyzed in 40 independent plaques. HO-1 (fold-change 1.93, 95%CI 1.04 to 3.94, P=0.040) and CD163 (1.58, 1.11 to 2.40, P=0.013) mRNAs were again induced, and also HO-1 protein was overexpressed in symptomatic plaques (4.38, 1.54 to 12.20, P=0.024). The expression of HO-1 and CD163 correlated with tissue iron content but iron itself was not associated with the symptom status.


CONCLUSIONS
Symptomatic plaques show overexpression of CD163 and HO-1 both in intraindividual and interindividual comparison. Their expression correlates with iron deposits but asymptomatic and symptomatic plaques from isolated patients do not differ in macroscopic hemorrhages or iron deposits. We suggest that symptomatic plaques show a more pronounced induction of CD163 and HO-1 in response to plaque hemorrhages.
Ijäs
Petra
P
Department of Neurology, Helsinki University Central Hospital, Finland. petra.ijas@hus.fi
Nuotio
Krista
K
Saksi
Jani
J
Soinne
Lauri
L
Saimanen
Eija
E
Karjalainen-Lindsberg
Marja-Liisa
ML
Salonen
Oili
O
Sarna
Seppo
S
Tuimala
Jarno
J
Kovanen
Petri T
PT
Kaste
Markku
M
Lindsberg
Perttu J
PJ
D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism*; D016893:Carotid Stenosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D004247:DNA / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006418:Heme / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006470:Hemorrhage; D006801:Humans; D007501:Iron / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D006418:Heme; D004247:DNA; D007501:Iron; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1