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. METHODS AND 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.
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. METHODS AND 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.
Authors: Lasse Folkersen; Jonas Persson; Johan Ekstrand; Hanna E Agardh; Göran K Hansson; Anders Gabrielsen; Ulf Hedin; Gabrielle Paulsson-Berne Journal: Mol Med Date: 2012-05-09 Impact factor: 6.354
Authors: Alexandra Kadl; Akshaya K Meher; Poonam R Sharma; Monica Y Lee; Amanda C Doran; Scott R Johnstone; Michael R Elliott; Florian Gruber; Jenny Han; Wenshu Chen; Thomas Kensler; Kodi S Ravichandran; Brant E Isakson; Brian R Wamhoff; Norbert Leitinger Journal: Circ Res Date: 2010-07-22 Impact factor: 17.367
Authors: Christian A Gleissner; Iftach Shaked; Christian Erbel; Dittmar Böckler; Hugo A Katus; Klaus Ley Journal: Circ Res Date: 2009-11-12 Impact factor: 17.367
Authors: Jani Saksi; Petra Ijäs; Krista Nuotio; Riitta Sonninen; Lauri Soinne; Oili Salonen; Eija Saimanen; Jarno Tuimala; Erno M Lehtonen-Smeds; Markku Kaste; Petri T Kovanen; Perttu J Lindsberg Journal: J Mol Med (Berl) Date: 2011-05-24 Impact factor: 4.599
Authors: Peter R Sinnaeve; Mark P Donahue; Peter Grass; David Seo; Jacky Vonderscher; Salah-Dine Chibout; William E Kraus; Michael Sketch; Charlotte Nelson; Geoffrey S Ginsburg; Pascal J Goldschmidt-Clermont; Christopher B Granger Journal: PLoS One Date: 2009-09-14 Impact factor: 3.240