Human urinary kininogenase reduces the endothelial injury by inhibiting Pyk2/MCU pathway - 09/10/21
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Abstract |
The injury of endothelial cells is one of the initiating factors in restenosis after endovascular treatment. Human urinary kallidinogenase (HUK) is a tissue kallikrein which is used for ischemia-reperfusion injury treatment. Studies have shown that HUK may be a potential therapeutic agent to prevent stenosis after vascular injury, however, the precise mechanisms have not been fully established. This study is to investigate whether HUK can protect endothelial cells after balloon injury or H2O2-induced endothelial cell damage through the proline-rich tyrosine kinase 2 (Pyk2)/mitochondrial calcium uniporter (MCU) pathway. Intimal hyperplasia, a decrease of pinocytotic vesicles and cell apoptosis were found in the common carotid artery balloon injury and H2O2-induced endothelial cell damage, Pyk2/MCU was also up-regulated in such pathological process. HUK could prevent these injuries partially via the bradykinin B2 receptor by inhibiting Pyk2/MCU pathway, which prevented the mitochondrial damage, maintained calcium balance, and eventually inhibited cell apoptosis. Furthermore, MCU expression was not markedly increased if Pyk2 was suppressed by shRNA technique in the H2O2 treatment group, and cell viability was significantly better than H2O2-treated only. In short, our results indicate that the Pyk2/MCU pathway is involved in endothelial injury induced by balloon injury or H2O2-induced endothelial cell damage. HUK plays an protective role by inhibiting the Pyk2/MCU pathway in the endothelial injury.
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Highlights |
• | Pyk2/MCU pathway was upregulated in rat common carotid artery balloon injury. |
• | Pyk2/MCU pathway was activated in H2O2-induced endothelial cell damage. |
• | Pyk2 suppression could protect endothelial cells from H2O2 injury. |
• | HUK protected endothelial cells by inhibiting Pyk2/MCU pathway partially through B2R. |
Keywords : Human urinary kininogenase, Endothelial injury, Pyk2, MCU, Balloon injury, Hydrogen peroxide
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Vol 143
Article 112165- novembre 2021 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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