Transforming growth factor-betas and CD105 expression in calcification and bone formation in human atherosclerotic lesions.
OBJECTIVE
To investigate the expression and localisation of transforming growth factor betas (TGF beta s) and their receptor CD105 (endoglin) in relation to calcification and bone formation in atherosclerotic lesions of human carotid arteries.


BACKGROUND
The TGF beta family regulates cellular growth, differentiation and angiogenesis and plays a key role in enchondral bone formation. CD105 is part of the TGF beta receptor complex preferentially expressed on endothelial cells (EC).


METHODS
Immunohistochemical methods were used to determine the localisation of TGF beta isoforms 1, 2 and 3 and their spatial expression patterns in relation to calcification and bone formation in atherosclerotic lesions. Cellular sources of TGF beta s and CD105 were assessed using cell-type specific antibodies.


RESULTS
There was marked variability in TGF beta expression in different cell types associated with calcification. Smooth muscle cells (SMC) in the atheroma cap showed higher levels of TGF beta 3 and 2 than 1, but in the deep musculoelastic intima there were higher levels of TGF beta 1 and alpha-actin. All three TGF beta isoforms were expressed in monocyte-macro-phages. Giant cells associated with calcifications showed intense staining for TGF beta 2. TGF beta 1 was most strongly expressed on matrix and cells associated with bone formation. CD105 expression on SMCs and monocyte-macrophages was lower on cells in close association with calcification. SMCs associated with bone formation expressed high levels of CD105.


CONCLUSIONS
The different TGF beta isoforms exhibit distinct but overlapping patterns of expression, and support the hypothesis that they are involved in the process of calcification and bone formation in human atherosclerotic lesions. Lower expression of CD105 on cells associated with calcification may represent their state of lower responsiveness to TGF beta s.
Jeziorska
M
M
Department of Pathological Sciences, Medical School, University of Manchester, Manchester M13 9PT, UK. maria.jeziorska@man.ac.uk
D015703:Antigens, CD; D001161:Arteriosclerosis / Q000473:pathology*; D002114:Calcinosis / Q000473:pathology*; D002339:Carotid Arteries / Q000473:pathology; D016893:Carotid Stenosis / Q000473:pathology; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000473:pathology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D009999:Ossification, Heterotopic / Q000473:pathology*; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta / Q000032:analysis*; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis*
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; D019010:Vascular Cell Adhesion Molecule-1