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Published on: February 15, 2022
MMP-14 promotes VSMC migration via up-regulating CD44 expression in cardiac allograft vasculopathy
Daliang Yan1, Xiaojuan Liu2, Lu Hua3
1Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PR China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu 226001, PR China.
Abstract:
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.
Insights
Matrix metalloproteinase-14 (MMP-14) interacts with CD44 in heart transplants, driving vascular smooth muscle cell migration. Inhibiting this MMP-14/CD44 complex offers a new target for preventing cardiac allograft vasculopathy (CAV).
Area of Science:
- Immunology
- Molecular Biology
- Cardiovascular Research
Background:
- Cardiac allograft vasculopathy (CAV) is a primary cause of late mortality in heart transplant recipients.
- Matrix metalloproteinase-14 (MMP-14) is implicated in coronary vascular lesions of transplanted hearts, but its precise mechanism remains unclear.
Purpose of the Study:
- To elucidate the molecular mechanism of MMP-14 in cardiac allografts.
- To investigate the interaction between MMP-14 and CD44 in the context of CAV.
- To evaluate the therapeutic potential of targeting the MMP-14/CD44 complex.
Main Methods:
- Comparative analysis of MMP-14 expression in isografts versus allografts.
- Investigation of MMP-14 and CD44 interaction in cardiac allografts.
- Assessment of MMP-14/CD44 complex effects on pro-MMP-9 activation and vascular smooth muscle cell (VSMC) migration using a rat VSMC TNF-α treated model.
Main Results:
- MMP-14 expression differs between isografts and allografts.
- A significant interaction between MMP-14 and CD44 was identified in allografts.
- Intervention targeting the MMP-14/CD44 complex effectively inhibited VSMC migration.
Conclusions:
- The MMP-14/CD44 complex plays a crucial role in mediating VSMC migration after cardiac transplantation.
- Targeting the MMP-14/CD44 interaction presents a promising therapeutic strategy for preventing and treating CAV.
