February 14, 2013

Cell connections key in valve disease

A protein that connects cells together participates in the calcification that occurs in heart valve disease.

The calcification (hardening) that occurs in heart valve disease has been associated with a pathological change in the behavior of valve interstitial cells, but very few markers of this process are known.


W. David Merryman, Ph.D., assistant professor of Biomedical Engineering, and colleagues have now identified a role for cadherin-11 – a cell-cell adhesion protein – in the generation of calcific nodules by cultured valve interstitial cells. They report in the January issue of Arteriosclerosis, Thrombosis, and Vascular Biology that TGF-beta1 treatment of valve cells – shown previously to activate the process that leads to calcification – increases expression of cadherin-11. Knocking down cadherin-11 prevents calcific nodule formation. The researchers further demonstrate that cadherin-11 is enriched in human calcified valve specimens.

The findings suggest that cell-cell connections – mediated by cadherin-11 – are required to generate the tension required for calcific nodule formation. Cadherin-11 will provide a useful tool for understanding the pathogenesis of heart valve disease and may be a target for molecular imaging strategies designed to “see” valve disease in its earliest stages.

This research was supported by grants from the American Heart Association and the National Institutes of Health (HL094707).