TY - JOUR
T1 - Increased CD74 expression in human atherosclerotic plaques
T2 - Contribution to inflammatory responses in vascular cells
AU - Martín-Ventura, José Luis
AU - Madrigal-Matute, Julio
AU - Muñoz-Garcia, Begoña
AU - Blanco-Colio, Luis Miguel
AU - Van Oostrom, Melany
AU - Zalba, Guillermo
AU - Fortuño, Ana
AU - Gomez-Guerrero, Carmen
AU - Ortega, Luis
AU - Ortiz, Alberto
AU - Diez, Javier
AU - Egido, Jesús
N1 - Funding Information:
This work was supported by the Spanish Ministerio de Ciencia y Tecnología (SAF2007/63648), Educación y Ciencia (SAF2007-62533), Fundacion Ramon Areces, CAM (S2006/ GEN-0247), Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, Redes RECAVA (RD06/0014/0035; RD06/ 0014/0008) REDinREN/RD06/0016 and European Network (HEALTH F2-2008-200647), and European Union (InGenious HyperCare, grant LSHM-CT-2006-037093). Programa Intensi-ficación Actividad Investigadora Sistema Nacional de Salud ISCIII/CM to A.O. This project was also funded through the agreement between the Foundation for Applied Medical Research (FIMA) and ‘UTE project CIMA’.
PY - 2009/8
Y1 - 2009/8
N2 - AimsThe purpose of this study was to analyse the expression of CD74 in human atherosclerotic plaques and peripheral blood mononuclear cells (PBMC) as well as its potential participation in proinflammatory responses in cultured human vascular smooth muscle cells (VSMC).Methods and resultsCD74 expression was analysed in human atherosclerotic plaques (immunohistochemistry), PBMC (real-time PCR), and human aortic VSMC (real-time PCR and western blotting). Nuclear factor-κB (NF-κB) activation was assessed by southwestern histochemistry and electrophoretic mobility shift assay. Monocyte chemoattractant protein-1 (MCP-1) levels were studied by both real-time PCR and enzyme-linked immunosorbent assay. CD74 immunostaining was increased in the inflammatory vs. the fibrous region of atherosclerotic plaques (n = 70, 18.2 ± 1.3 vs. 7.8 ± 0.6 positive staining/mm2, P < 0.001). CD74 colocalized with the transcription factor NF-κB in both VSMC and macrophages. In cultured VSMC, CD74 expression was induced by interferon γ (IFNγ). Incubation with an agonistic anti-CD74 antibody or with IFNγ elicited MCP-1 expression, which was prevented by AKT and γ-secretase inhibitors. Moreover, CD74 small-interfering RNA decreased NF-κB activation and MCP-1 production induced by IFNγ in VSMC. Finally, CD74 mRNA levels in PBMC from patients with carotid stenosis were higher than in healthy subjects (n = 20, 3 ± 0.5 vs. 2 ± 0.5 AU, P < 0.001). Additionally, a linear trend between CD74 mRNA expression tertiles and intima-media thickness (IMT) was observed in PBMC from asymptomatic subjects (n = 185, P < 0.001).ConclusionCD74 levels are increased in plaques and PBMC from patients with carotid stenosis and are associated with IMT in subjects free from clinical cardiovascular diseases. CD74 could be a novel therapeutic target to decrease the inflammatory response in atherosclerosis.
AB - AimsThe purpose of this study was to analyse the expression of CD74 in human atherosclerotic plaques and peripheral blood mononuclear cells (PBMC) as well as its potential participation in proinflammatory responses in cultured human vascular smooth muscle cells (VSMC).Methods and resultsCD74 expression was analysed in human atherosclerotic plaques (immunohistochemistry), PBMC (real-time PCR), and human aortic VSMC (real-time PCR and western blotting). Nuclear factor-κB (NF-κB) activation was assessed by southwestern histochemistry and electrophoretic mobility shift assay. Monocyte chemoattractant protein-1 (MCP-1) levels were studied by both real-time PCR and enzyme-linked immunosorbent assay. CD74 immunostaining was increased in the inflammatory vs. the fibrous region of atherosclerotic plaques (n = 70, 18.2 ± 1.3 vs. 7.8 ± 0.6 positive staining/mm2, P < 0.001). CD74 colocalized with the transcription factor NF-κB in both VSMC and macrophages. In cultured VSMC, CD74 expression was induced by interferon γ (IFNγ). Incubation with an agonistic anti-CD74 antibody or with IFNγ elicited MCP-1 expression, which was prevented by AKT and γ-secretase inhibitors. Moreover, CD74 small-interfering RNA decreased NF-κB activation and MCP-1 production induced by IFNγ in VSMC. Finally, CD74 mRNA levels in PBMC from patients with carotid stenosis were higher than in healthy subjects (n = 20, 3 ± 0.5 vs. 2 ± 0.5 AU, P < 0.001). Additionally, a linear trend between CD74 mRNA expression tertiles and intima-media thickness (IMT) was observed in PBMC from asymptomatic subjects (n = 185, P < 0.001).ConclusionCD74 levels are increased in plaques and PBMC from patients with carotid stenosis and are associated with IMT in subjects free from clinical cardiovascular diseases. CD74 could be a novel therapeutic target to decrease the inflammatory response in atherosclerosis.
KW - Atherosclerosis
KW - Biomarkers
KW - Carotid stenosis
KW - Inflammation
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U2 - 10.1093/cvr/cvp141
DO - 10.1093/cvr/cvp141
M3 - Article
C2 - 19423618
AN - SCOPUS:67651124959
VL - 83
SP - 586
EP - 594
JO - Cardiovascular Research
JF - Cardiovascular Research
SN - 0008-6363
IS - 3
ER -