MMP-14 promotes VSMC migration via up-regulating CD44 expression in cardiac allograft vasculopathy

Cardiac allograft vasculopathy (CAV) was the leading cause of late death in heart transplantation recipients. Matrix metalloproteinase-14 (MMP-14), as a member of the MMPs family, has been reported to play a vital role in coronary vascular lesions of allotransplanted hearts. However, concrete mechanism is still unclear. Herein, we showed that the expression of MMP-14 was different between isografts and allografts. Interestingly, we found MMP-14 could interact with CD44 in allografts. Cluster of differentiation 44 (CD44), as a cell adhesion receptor and is involved in cell migration, caused our interest in MMP-14/CD44 complex in allografts. Then we analyzed the effect of MMP-14/CD44 complex on pro-MMP-9 activation and vascular smooth muscle cell (VSMC) migration in rat VSMC TNF-α treated model. Then, we further found intervention of MMP-14/CD44 complex could inhibit VSMC migration. Our results elucidate the molecular mechanism of VSMC migration after cardiac transplantation and provide theoretical basis for seeking new specific drug targets for CAV prevention and treatment.