PMID- 19423618
OWN - NLM
STAT- MEDLINE
DCOM- 20090917
LR  - 20220408
IS  - 1755-3245 (Electronic)
IS  - 0008-6363 (Linking)
VI  - 83
IP  - 3
DP  - 2009 Aug 1
TI  - Increased CD74 expression in human atherosclerotic plaques: contribution to 
      inflammatory responses in vascular cells.
PG  - 586-94
LID - 10.1093/cvr/cvp141 [doi]
AB  - AIMS: The 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 RESULTS: CD74 expression was 
      analysed in human atherosclerotic plaques (immunohistochemistry), PBMC (real-time 
      PCR), and human aortic VSMC (real-time PCR and western blotting). Nuclear 
      factor-kappaB (NF-kappaB) 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-kappaB in both VSMC and macrophages. In cultured VSMC, CD74 expression was 
      induced by interferon gamma (IFNgamma). Incubation with an agonistic anti-CD74 
      antibody or with IFNgamma elicited MCP-1 expression, which was prevented by AKT 
      and gamma-secretase inhibitors. Moreover, CD74 small-interfering RNA decreased 
      NF-kappaB activation and MCP-1 production induced by IFNgamma 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). 
      CONCLUSION: CD74 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.
FAU - Martin-Ventura, Jose Luis
AU  - Martin-Ventura JL
AD  - Renal and Vascular Research Lab, Fundacion Jimenez Diaz, Autonoma University, 
      Madrid, Spain. jlmartin@fjd.es
FAU - Madrigal-Matute, Julio
AU  - Madrigal-Matute J
FAU - Munoz-Garcia, Begona
AU  - Munoz-Garcia B
FAU - Blanco-Colio, Luis Miguel
AU  - Blanco-Colio LM
FAU - Van Oostrom, Melany
AU  - Van Oostrom M
FAU - Zalba, Guillermo
AU  - Zalba G
FAU - Fortuno, Ana
AU  - Fortuno A
FAU - Gomez-Guerrero, Carmen
AU  - Gomez-Guerrero C
FAU - Ortega, Luis
AU  - Ortega L
FAU - Ortiz, Alberto
AU  - Ortiz A
FAU - Diez, Javier
AU  - Diez J
FAU - Egido, Jesus
AU  - Egido J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090507
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Antigens, Differentiation, B-Lymphocyte)
RN  - 0 (Biomarkers)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (invariant chain)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Antigens, Differentiation, B-Lymphocyte/blood/genetics/*metabolism
MH  - Biomarkers/metabolism
MH  - Carotid Arteries/*immunology/pathology/surgery
MH  - Carotid Stenosis/*immunology/pathology/surgery
MH  - Case-Control Studies
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Endarterectomy, Carotid
MH  - Fibrosis
MH  - Histocompatibility Antigens Class II/blood/genetics/*metabolism
MH  - Humans
MH  - Inflammation/*immunology/pathology
MH  - Inflammation Mediators/blood/*metabolism
MH  - Interferon-gamma/metabolism
MH  - Leukocytes, Mononuclear/immunology
MH  - Macrophages/immunology
MH  - Muscle, Smooth, Vascular/*immunology/pathology/surgery
MH  - Myocytes, Smooth Muscle/*immunology/pathology
MH  - NF-kappa B/metabolism
MH  - RNA Interference
MH  - Recombinant Proteins/metabolism
MH  - Severity of Illness Index
MH  - Time Factors
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Tunica Intima/immunology
MH  - Tunica Media/immunology
MH  - Up-Regulation
EDAT- 2009/05/09 09:00
MHDA- 2009/09/18 06:00
CRDT- 2009/05/09 09:00
PHST- 2009/05/09 09:00 [entrez]
PHST- 2009/05/09 09:00 [pubmed]
PHST- 2009/09/18 06:00 [medline]
AID - cvp141 [pii]
AID - 10.1093/cvr/cvp141 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2009 Aug 1;83(3):586-94. doi: 10.1093/cvr/cvp141. Epub 2009 May 
      7.