Urokinase-type plasminogen activator receptor is associated with macrophages and plaque rupture in symptomatic carotid atherosclerosis.
Journal article, 2008
There is a strong correlation between macrophage infiltration and plaque instability in recently symptomatic carotid atherosclerotic plaques, and it is hypothesised that mechanisms related to macrophages may be involved in plaque vulnerability and rupture. We previously found high expression of urokinase-type plasminogen activator receptor (UPAR) in human macrophages. The aim of this study was to investigate whether UPAR co-localises with macrophages in symptomatic carotid plaques, and whether UPAR expression is associated with plaque rupture. Real-time RT-PCR assays showed that UPAR expression levels were high in monocyte-derived macrophages and in carotid endarterectomies compared with a tissue panel. Serial transverse sections were prepared from carotid endarterectomies from 12 symptomatic patients, and analyzed with immunohistochemical staining for UPAR and for CD68-positive macrophages, and with histopathological assessment. UPAR co-localised with CD68-positive macrophages, with a high correlation (r=0.90, p<0.001) between immunostained areas in 12 carotid endarterectomies from symptomatic patients. High degrees of UPAR and CD68 staining were found in sections around the bifurcation level where rupture was most common, while low degrees of staining were found in sections of the common carotid artery end of the endarterectomy (p<0.05). Higher degrees of UPAR staining were observed in ruptured plaque sections compared with non-ruptured sections. In conclusion, UPAR was highly expressed in monocyte-derived macrophages and in symptomatic carotid plaques, UPAR co-localised with macrophages in carotid symptomatic plaques and UPAR was predominantly found in ruptured plaque segments. These findings support the hypothesis that UPAR is related to plaque rupture in symptomatic atherosclerotic lesions.
complications
metabolism
Antigens
Middle Aged
genetics
metabolism
CD
Differentiation
Cells
Humans
pathology
Carotid Stenosis
Carotid
Cultured
complications
Male
pathology
Endarterectomy
Receptors
Cell Surface
Myelomonocytic
Protein Transport
Female
Aged
Gene Expression Regulation
Carotid Artery Diseases
Aged
Macrophages
metabolism
genetics
Antigens
pathology
80 and over
metabolism
genetics
Author
Per-Arne Svensson
University of Gothenburg
Fredrik J. Olson
University of Gothenburg
Daniel Hägg
University of Gothenburg
Mikael Ryndel
University of Gothenburg
Olov Wiklund
University of Gothenburg
Lars Karlström
University of Gothenburg
Johannes Hulthe
University of Gothenburg
Lena M S Carlsson
University of Gothenburg
Björn Fagerberg
University of Gothenburg
International Journal of Molecular Medicine
1107-3756 (ISSN) 1791244x (eISSN)
Vol. 22 4 459-64Subject Categories
MEDICAL AND HEALTH SCIENCES
DOI
10.3892/ijmm_00000043
PubMed
18813852