Oxygen-generating microparticles downregulate HIF-1α expression, increase cardiac contractility, and mitigate ischemic injury

产氧微粒下调HIF-1α表达、增强心脏收缩力、减轻缺血性损伤

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作者:Kalpana Mandal, Sivakoti Sangabathuni, Reihaneh Haghniaz, Satoru Kawakita, Marvin Mecwan, Aya Nakayama, Xuexiang Zhang, Masoud Edalati, Wei Huang, Ana Lopez Hernandez, Vadim Jucaud, Mehmet R Dokmeci, Ali Khademhosseini

Significance

Oxygen-releasing microparticles can reduce myocardial ischemia, allograft rejection, or irregular heartbeats after heart transplantation. Here we present biodegradable oxygen-releasing microparticles that are capable of sustained oxygen release for more than 24 hrs. We then studied the impact of sustained oxygen release from microparticles on gene expresseion and cardiac cell and tissue function. Previous studies have not measured cardiac tissue or cell mechanics during hypoxia, which is important for understanding proper cardiac function and beating. Using traction force microscopy and an engineered tissue-on-a-chip, we demonstrated that our oxygen-releasing microparticles improve cell and tissue contractility during hypoxia while downregulating the HIF-1α expression level. Finally, using the microparticles, we showed reduced myocardial injuries in rabbit heart tissue, confirming the potential of the particles to be used for organ transplantation or tissue engineering.

Statement of significance

Oxygen-releasing microparticles can reduce myocardial ischemia, allograft rejection, or irregular heartbeats after heart transplantation. Here we present biodegradable oxygen-releasing microparticles that are capable of sustained oxygen release for more than 24 hrs. We then studied the impact of sustained oxygen release from microparticles on gene expresseion and cardiac cell and tissue function. Previous studies have not measured cardiac tissue or cell mechanics during hypoxia, which is important for understanding proper cardiac function and beating. Using traction force microscopy and an engineered tissue-on-a-chip, we demonstrated that our oxygen-releasing microparticles improve cell and tissue contractility during hypoxia while downregulating the HIF-1α expression level. Finally, using the microparticles, we showed reduced myocardial injuries in rabbit heart tissue, confirming the potential of the particles to be used for organ transplantation or tissue engineering.

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