Co‑expression of tissue kallikrein 1 and tissue inhibitor of matrix metalloproteinase 1 improves myocardial ischemia‑reperfusion injury by promoting angiogenesis and inhibiting oxidative stress

Huang,Shujie; Chen,Meixian; Yu,Huizhen; Lin,Kaiyang; Guo,Yansong; Zhu,Pengli

doi:10.3892/mmr.2020.11805

Co‑expression of tissue kallikrein 1 and tissue inhibitor of matrix metalloproteinase 1 improves myocardial ischemia‑reperfusion injury by promoting angiogenesis and inhibiting oxidative stress

Authors:
- Shujie Huang
- Meixian Chen
- Huizhen Yu
- Kaiyang Lin
- Yansong Guo
- Pengli Zhu
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Affiliations: Department of Cardiology, Fujian Provincial Hospital, Fuzhou, Fujian 350001, P.R. China, Department of Cardiology, The 900th Hospital of Joint Logistics Support Force of People's Liberation Army, Fuzhou, Fujian 350025, P.R. China, Department of Cardiology, Fujian Provincial Hospital Jinshan Branch, Fuzhou, Fujian 350028, P.R. China
Published online on: December 22, 2020 https://doi.org/10.3892/mmr.2020.11805
Article Number: 166
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Myocardial ischemia/reperfusion (I/R) injury is a serious complication of reperfusion therapy for myocardial infarction. At present, there is not an effective treatment strategy available for myocardial I/R. The present study aimed to investigate the effects of human tissue kallikrein 1 (hTK1) and human tissue inhibitors of matrix metalloproteinase 1 (hTIMP1) gene co‑expression on myocardial I/R injury. A rat model of myocardial I/R injury and a cell model with hypoxia/reoxygenation (H/R) treatment in cardiac microvascular endothelial cells (CMVECs) were established, and treated with adenovirus (Ad)‑hTK1/hTIMP1. Following which, histological and triphenyl‑tetrazolium‑chloride staining assays were performed. Cardiac function was tested by echocardiographic measurement. The serum levels of oxidative stress biomarkers in rats and the intracellular reactive oxygen species (ROS) levels in CMVECs were measured. Additionally, experiments, including immunostaining, reverse transcription‑quantitative PCR, western blotting, and MTT, wound healing, Transwell and tube formation assays were also performed. The results of the present study demonstrated that Ad‑hTK1/hTIMP1 alleviated myocardial injury and improved cardiac function in myocardial I/R model rats. Ad‑hTK1/hTIMP1 also significantly enhanced microvessel formation, decreased matrix metalloproteinase (MMP)2 and MMP9 expression, and reduced oxidative stress in myocardial I/R model rats. Furthermore, Ad‑hTK1/hTIMP1 significantly enhanced proliferation, migration and tube formation in H/R‑treated CMVECs. Additionally, Ad‑hTK1/hTIMP1 significantly decreased intracellular ROS production and γ‑H2A.X variant histone expression levels in H/R‑treated CMVECs. In conclusion, the results of the present study demonstrated that co‑expression of hTK1 and hTIMP1 genes displayed significant protective effects on myocardial I/R injury by promoting angiogenesis and suppressing oxidative stress; therefore, co‑expression of hTK1 and hTIMP1 may serve as a potential therapeutic strategy for myocardial I/R injury.

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