A heart valve lacking Chm-I fills with vascularized muck.


Heart valves achieve an impressive balancing act—they block large vessels but only temporarily. The blockage becomes more permanent in rheumatic valvular heart disease (VHD) when tiny, new blood vessels clog the valve. Now, Masatoyo Yoshioka, Keiichi Fukuda (Keio University, Tokyo, Japan), and colleagues find that the antiangiogenic chondromodulin-I (Chm-I) normally keeps heart valves clear of new blood vessels, and its loss is associated with VHD.

The finding was waiting to be made, says Fukuda, because “nobody was interested in studying this. Valvular heart disease is common, but most cardiologists think this is a disease for cardiac surgeons, and the surgeons only do operations.”

Chm-I was already known as an antiangiogenic factor in avascular tissues of the eye and cartilage. The Tokyo group found that it was expressed in heart valves, and its deletion led to valves that were double the normal size and with almost 14-fold more capillaries. A similar pattern of Chm-I loss and new vessel growth was seen in mouse models of VHD and atherosclerosis.

Mesenchymal cells from normal valves secreted Chm-I in vitro, and both this Chm-I and recombinant Chm-I had antiangiogenic activity. Valves may need constant protection against angiogenesis because they are under mechanical stress that could easily initiate the formation of new blood vessels. In some individuals this stress may compromise the mesenchymal cells, and thus begin the disease process that Fukuda hopes to combat with exogenous Chm-I.


Yoshioka, M., et al.
Nat. Med.