Increased CD74 expression in human atherosclerotic plaques: Contribution to inflammatory responses in vascular cells

José Luis Martín-Ventura, Julio Madrigal-Matute, Begoña Muñoz-Garcia, Luis Miguel Blanco-Colio, Melany Van Oostrom, Guillermo Zalba, Ana Fortuño, Carmen Gomez-Guerrero, Luis Ortega, Alberto Ortiz, Javier Diez, Jesús Egido

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)586-594
Number of pages9
JournalCardiovascular research
Volume83
Issue number3
DOIs
StatePublished - Aug 1 2009
Externally publishedYes

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Atherosclerotic Plaques
Vascular Smooth Muscle
Smooth Muscle Myocytes
Blood Vessels
Blood Cells
Chemokine CCL2
Interferons
Real-Time Polymerase Chain Reaction
Carotid Stenosis
Amyloid Precursor Protein Secretases
Messenger RNA
Electrophoretic Mobility Shift Assay
Small Interfering RNA
Anti-Idiotypic Antibodies
Atherosclerosis
Healthy Volunteers
Transcription Factors
Cardiovascular Diseases
Western Blotting
Enzyme-Linked Immunosorbent Assay

Keywords

  • Atherosclerosis
  • Biomarkers
  • Carotid stenosis
  • Inflammation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Martín-Ventura, J. L., Madrigal-Matute, J., Muñoz-Garcia, B., Blanco-Colio, L. M., Van Oostrom, M., Zalba, G., ... Egido, J. (2009). Increased CD74 expression in human atherosclerotic plaques: Contribution to inflammatory responses in vascular cells. Cardiovascular research, 83(3), 586-594. https://doi.org/10.1093/cvr/cvp141

Increased CD74 expression in human atherosclerotic plaques : Contribution to inflammatory responses in vascular cells. / Martín-Ventura, José Luis; Madrigal-Matute, Julio; Muñoz-Garcia, Begoña; Blanco-Colio, Luis Miguel; Van Oostrom, Melany; Zalba, Guillermo; Fortuño, Ana; Gomez-Guerrero, Carmen; Ortega, Luis; Ortiz, Alberto; Diez, Javier; Egido, Jesús.

In: Cardiovascular research, Vol. 83, No. 3, 01.08.2009, p. 586-594.

Research output: Contribution to journalArticle

Martín-Ventura, JL, Madrigal-Matute, J, Muñoz-Garcia, B, Blanco-Colio, LM, Van Oostrom, M, Zalba, G, Fortuño, A, Gomez-Guerrero, C, Ortega, L, Ortiz, A, Diez, J & Egido, J 2009, 'Increased CD74 expression in human atherosclerotic plaques: Contribution to inflammatory responses in vascular cells', Cardiovascular research, vol. 83, no. 3, pp. 586-594. https://doi.org/10.1093/cvr/cvp141
Martín-Ventura, José Luis ; Madrigal-Matute, Julio ; Muñoz-Garcia, Begoña ; Blanco-Colio, Luis Miguel ; Van Oostrom, Melany ; Zalba, Guillermo ; Fortuño, Ana ; Gomez-Guerrero, Carmen ; Ortega, Luis ; Ortiz, Alberto ; Diez, Javier ; Egido, Jesús. / Increased CD74 expression in human atherosclerotic plaques : Contribution to inflammatory responses in vascular cells. In: Cardiovascular research. 2009 ; Vol. 83, No. 3. pp. 586-594.
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abstract = "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.",
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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

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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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