Journal of Atherosclerosis and Thrombosis Vol.13, No.2
Significant Expression of Endoglin (CD105), TGFβ-1 and TGFβR-2
in the Atherosclerotic Aorta: An Immunohistological Study
Meihua Piao and Osamu Tokunaga
Department of Pathology and Biodefense, Saga University Faculty of Medicine, Saga, Japan.
To date, the glycoprotein endoglin and its receptor complex, formed between TGFβ and TGFβR-2,
have been studied in tumor angiogenesis. The purpose of this study is to investigate the expression
profile of endoglin and its receptor complex in human atherosclerotic lesions, and compare it to that
in non-atherosclerotic tissues. Twenty-six atherosclerotic lesions and twenty-six non-atherosclerotic
aortic tissues were collected from thirty-six autopsy cases. Indirect immunohistochemical staining
was performed to detect the presence of endoglin, TGFβ-1, and TGFβR-2 proteins in aortic tissues.
Endoglin expression was observed in smooth muscle cells (SMC), macrophages and endothelial cells
of aortic atherosclerotic lesions. The levels of TGFβ-1 and TGFβR-2 were increased in the intimal
matrices, smooth muscle cells, and macrophages, as well as in endothelial cells. The expression levels
of endoglin, TGFβ-1, and TGFβR-2 were higher in atherosclerotic lesions than in non-atheroscle-
rotic aortic tissues (p＜0.0001), and there was a correlation among the expression of endoglin, TGFβ
-1, and TGFβR-2 in atherosclerotic aortic lesions (p＜0.001). Endoglin or its receptor complex may
participate in the atherogenesis.
J Atheroscler Thromb, 2006; 13:82-89.
Key words; Endoglin (CD105), TGFβ-1, TGFβR-2, Atherosclerosis
Endoglin (CD105), a cell membrane glycopro-
tein, is a homodimeric transmembrane receptor for
transforming growth factor (TGF)β-1 and TGFβ3,
and forms a TGF beta receptor complex on endotheli-
al cells1). Endoglin can bind TGFβ-1 and TGFβ-3
with high affinity and appears to do so only in the
presence of TGFβR-22, 3). So far, the role of endoglin
in angiogenesis has been studied primarily in tumor
endothelial cells of various organs4-8). A marked in-
crease in the expression of endoglin has been demon-
strated on the surface of vascular endothelial cells9). A
recent study which investigated patients with coronary
artery disease suggested that endoglin may be impor-
tant in the pathogenesis of atherosclerotic disease10).
There have been some reports that endoglin is ex-
pressed in atherosclerotic plaques, such as in smooth
muscle cells11, 12) or in calcification-associated athero-
sclerotic lesions13). However, to the best of our knowl-
edge, the expression profiles of endoglin in association
with TGFβ and its receptor, which compose a func-
tional receptor complex, have not been studied in hu-
man atherosclerotic plaques.
TGFβ has marked effects on cell proliferation,
differentiation, adhesion, migration, and extracellular
matrix (ECM) production, as well as other activi-
ties14). The role of TGFβ in the pathogenesis of ath-
erosclerosis is being recognized. Its regulatory function
on the vessel wall is directed at the vascular SMCs, en-
dothelial cells and ECM. TGFβ-1 plays an important
role as an endogenous growth regulatory factor pro-
duced by the neointimal SMCs themselves during
progressive neointimal thickening after balloon angio-
plasty in an animal model15).The purpose of this study
is to examine the expression of endoglin with its re-
ceptor complex in atherosclerotic lesions using immu-
nohistochemistry and to evaluate its role in atherogen-
In fact, recent studies indicate that angiogenesis
Address for correspondence: Osamu Tokunaga, Department
of Pathology and Biodefense, Saga University Faculty of
Medicine, Saga 849-8501, Japan.
Received: August 22, 2005
Accepted for publication: December 8, 2005
Endoglin Expression in Atherosclerosis
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