title: Association between hemoglobin scavenger receptor and heme oxygenase-1-related anti-inflammatory mediators in human coronary stable and unstable plaques.
abstract: Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that is induced by intraplaque hemorrhage and degrades free heme and releases ferrous iron, which is rapidly sequestered by ferritin. In vitro studies have shown that binding of hemoglobin to hemoglobin scavenger receptor (CD163) induces HO-1 and the anti-inflammatory mediator interleukin (IL)-10. We immunohistochemically examined the relationship between CD163 expression in macrophages and intraplaque hemorrhage, HO-1, IL-10, and ferritin using coronary atherectomy specimens from patients with stable (SAP) or unstable angina pectoris (UAP). A total of 67 patients underwent atherectomy for SAP (n = 33) or UAP (n = 34). Samples were stained with antibodies against smooth muscle cells, macrophages, glycophorin-A (a protein specific to erythrocyte membranes), CD163, HO-1, IL-10, and ferritin. To identify cell types of HO-1-positive cells, double immunostaining was also performed. Double immunostaining for HO-1 and macrophages revealed that the vast majority of HO-1-positive cells were macrophages. Morphometric analysis demonstrated that CD163-positive macrophage score and the percentage of glycophorin-A-, HO-1-, IL-10-, and ferritin-positive areas were significantly higher in UAP than in SAP patients (CD163, P < .005; glycophorin-A, P < .0001; HO-1, P < .0001; IL-10, P < .005; ferritin, P = .0001). Moreover, CD163-positive macrophage score was positively associated with the percentage of glycophorin-A-, HO-1-, IL-10-, and ferritin-positive areas (glycophorin-A, r = 0.60, P < .0001; HO-1, r = 0.67, P < .0001; IL-10, r = 0.45, P < .0005; ferritin, r = 0.61, P < .0001). These findings suggest that enhanced expression of HO-1 and HO-1-related atheroprotective molecules plays an important role in exerting anti-inflammatory, antioxidant, and scavenging functions, which could contribute to plaque stabilization.
authors.affiliation: Department of Cardiology, Osaka City General Hospital, Osaka 534-0021, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Yunoki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inoue
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugioka
authors.forename: Masashi
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Mayumi
authors.initials: M
authors.lastname: Inaba
authors.forename: Satoko
authors.initials: S
authors.lastname: Wada
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ohsawa
authors.forename: Ryushi
authors.initials: R
authors.lastname: Komatsu
authors.forename: Akira
authors.initials: A
authors.lastname: Itoh
authors.forename: Kazuo
authors.initials: K
authors.lastname: Haze
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshiyama
authors.forename: Anton E
authors.initials: AE
authors.lastname: Becker
authors.forename: Makiko
authors.initials: M
authors.lastname: Ueda
authors.forename: Takahiko
authors.initials: T
authors.lastname: Naruko
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D017073:Atherectomy; D015415:Biomarkers / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006470:Hemorrhage / Q000150:complications / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051116:Receptors, Scavenger / Q000378:metabolism*; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; C508609:IL10 protein, human; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger; D016753:Interleukin-10; D051547:Heme Oxygenase-1
keywords: Angina; Heme oxygenase-1; Hemoglobin scavenger receptor; Intraplaque hemorrhage