Inhibition of the cyclophilin A-CD147 interaction attenuates right ventricular injury and dysfunction after acute pulmonary embolism in rats.

Acute pulmonary embolism (APE)-induced inflammation contributes to cardiomyocyte injury and dysfunction in the right ventricle (RV) of the heart. The interactions of cyclophilin A with its ligand extracellular matrix metalloproteinase inducer (EMMPRIN or CD147) may be involved in this inflammatory process. To this end, here we induced APE by intravenous injections of microspheres in Sprague-Dawley rats. We found that after the APE, cyclophilin A and CD147 levels increased synchronously in RV tissue following APE and peaked at 24 h. The cyclophilin A inhibitor cyclosporine A attenuated the APE-induced cyclophilin A levels, and a monoclonal antibody of CD147 (anti-CD147) abrogated the elevation of CD147 in the RV but not the increase of cyclophilin A. Importantly, treatment with cyclosporine A, anti-CD147, or both attenuated APE-induced increases in RV systolic pressure, plasma cardiac troponin-I (cTnI) concentrations, the RV/left ventricle diameter ratio, and the Tei index, measured by echocardiography 24 h after APE induction. These beneficial effects were associated with reduced RV neutrophil infiltration and prevention of matrix metalloproteinase 9 (MMP-9) and MMP-2 activation. These findings suggested that inhibiting the cyclophilin A-CD147 interaction attenuates APE-associated RV cardiomyocyte injury and dysfunction by suppressing inflammation. We further proposed that cyclophilin A and CD147 might participate in APE-induced pathological processes by partly activating the ERK1/2 kinase-nuclear factor-κB pathway. We conclude that the cyclophilin A-CD147 interaction may represent a potential therapeutic target for managing APE.

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