Transforming growth factor-βs and CD105 expression in calcification and bone formation in human atherosclerotic lesions

Summary

Objectives. To investigate the expression and localisation of transforming growth factor betas (TGFβs) and their receptor CD105 (endoglin) in relation to calcification and bone formation in atherosclerotic lesions of human carotid arteries. Background. The TGFβ family regulates cellular growth, differentiation and angiogenesis and plays a key role in enchondral bone formation. CD105 is part of the TGFβ receptor complex preferentially expressed on endothelial cells (EC). Methods. Immunohistochemical methods were used to determine the localisation of TGFβ isoforms 1, 2, and 3 and their spatial expression patterns in relation to calcification and bone formation in atherosclerotic lesions. Cellular sources of TGFβs and CD105 were assessed using cell-type specific antibodies. Results. There was marked variability in TGFβ expression in different cell types associated with calcification. Smooth muscle cells (SMC) in the atheroma cap showed higher levels of TGFβ3 and 2 than 1, but in the deep musculoelastic intima there were higher levels of TGFβ1 and α-actin. All three TGFβ isoforms were expressed in monocyte-macrophages. Giant cells associated with calcifications showed intense staining for TGFβ2. TGFβ1 was most strongly expressed on matric 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 TGFβ 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 TGFβs.