Key result
SP-8356 suppressed cell apoptosis and inflammatory response in pulmonary embolism-associated cardiac injury models by down-regulating MMP-9, p-ERK1/2, and p-P65 in a dose-dependent manner.
Why the study?
Because cyclophilin A-CD147 interaction and ERK1/2 signalling are implicated in acute pulmonary embolism and cardiac injury, this study evaluated the therapeutic effects of the CD147-cyclophilin inhibitor SP-8356.
Does SP-8356 reduce pulmonary embolism-associated cardiac injury in rat models?
Does SP-8356 reduce pulmonary embolism-associated cardiac injury in rat models?
SP-8356 attenuates pulmonary embolism-associated cardiac injury by suppressing apoptosis and inflammation via down-regulation of MMP-9, p-ERK1/2, and p-P65 in preclinical models.
SP-8356 may reduce PE cardiac injury in rodents; hypothesis-generating for CD147 inhibition in patients.
The cyclophilin A-CD147 interaction has been reported to be one of the most potential therapeutic targets for the treatment of acute pulmonary embolism. The signalling of extracellular signal-regulated kinase 1/2 (ERK1/2) was also reported in the pathogenesis of cardiac injury. Since SP-8356 is regarded as a novel Inhibitor of CD147-Cyclophilin, the study aimed to evaluate potential therapeutic effects of SP-8356 for pulmonary embolism-associated cardiac injury. Western blot and immunohistochemistry were carried out to analyse the expression of MMP-9, ERK1/2, phosphorylated ERK1/2 (p-ERK1/2), P65, p-P65, and CyA protein in PE cell and rat models under distinct conditions. Flow cytometry and TUNEL were carried out to examine the apoptosis of primary rat myocardiocytes and PE rat models under distinct conditions. CyA treatment on primary rat myocardiocytes remarkably raised the expression of MMP-9, p-ERK1/2 and p-P65 protein expression; SP8536 treatment effectively restored the CyA-induced up-regulation of MMP-9, p-ERK1/2 and p-P65 protein expression in primary rat myocardiocytes. Besides, flow cytometry analysis showed that SP8536 remarkably suppressed the CyA-induced elevation of cell apoptosis rate of primary rat myocardiocytes. Moreover, SP8536 notably diminished the abnormal elevation of right ventricular systolic pressure (RVSP), Troponin I and Myeloperoxidase activity in PE rat models. Furthermore, SP-8536 significantly restored the up-regulation of MMP-9, p-ERK1/2, p-P65, CyA protein and the cellular apoptosis in the PE rat model. Our study validated that SP-8356 could suppress cell apoptosis and inflammatory response via down-regulating the highly expressed MMP-9, p-ERK1/2, and p-P65 and MMP-9 in PE-associated cardiac injury in a dose-dependent manner.
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Zhou et al. (2021) studied Pulmonary embolism-associated cardiac injury. SP-8356 vs. Control/Vehicle was evaluated on Apoptosis and inflammatory response (expression of MMP-9, p-ERK1/2, p-P65, RVSP, Troponin I, Myeloperoxidase activity). SP-8356 suppressed cell apoptosis and inflammatory response in pulmonary embolism-associated cardiac injury models by down-regulating MMP-9, p-ERK1/2, and p-P65 in a dose-dependent manner.
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