Therapeutic CCR2 Blockade Prevents Inflammation and Alleviates Myxomatous Valve Disease in Marfan Syndrome

Myxomatous valve disease (MVD) can lead to cardiac dysfunction and heart failure, yet medical therapies are lacking. C-C chemokine receptor type 2 (CCR2)+ immune cell infiltration promotes mitral valve inflammation in a Marfan syndrome (MFS) mouse model. The CCR2 genetic knockout reduces inflammation with downregulated proteases and improved extracellular matrix integrity. Pharmacological inhibition of CCR2+ cell infiltration by RS504393 prevents the initiation and progression of MVD, indicated by restored protease expression, improved extracellular matrix organization, and reduced valve leaflet thickness in MFS mice. Thus, the CCR2 antagonist RS504393 is a promising therapy for the treatment of MVD in MFS.