eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
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4/2017
 
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abstract:
Experimental research

The influence of rapamycin on the early cardioprotective effect of hypoxic preconditioning on cardiomyocytes

Jiang Wang, YiLiyaer Maimaitili, Hong Zheng, Jin Yu, Hai Guo, Hai-Ping Ma, Chun-ling Chen

Arch Med Sci 2017; 13, 4: 947–955
Introduction: The purpose of this study was to examine the effects of rapamycin on the cardioprotective effect of hypoxic preconditioning (HPC) and on the mammalian target of rapamycin (mTOR)-mediated hypoxia-inducible factor 1 (HIF-1) signaling pathway.

Material and methods: Primary cardiomyocytes were isolated from rat pups and underwent rapamycin and/or HPC, followed by hypoxia/re-oxygenation (H/R) injury. Cell viability and cell injury were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, and qRT-PCR was used to measure HIF-1α and mTOR mRNA expression. A Langendorff heart perfusion model was conducted to observe the effect of rapamycin.

Results Rapamycin treatment nearly abolished the cardioprotective effect of HPC in cardiomyocytes, reduced cell viability (p = 0.007) and increased cell damage (p = 0.032). HIF-1α and mTOR mRNA expression increased in cardiomyocytes undergoing I/R injury within 2 h after HPC. After rapamycin treatment, mTOR mRNA expression and HPC-induced HIF-1α mRNA expression were both reduced (p < 0.001). A Langendorff heart perfusion model in rat hearts showed that rapamycin greatly attenuated the cardioprotective effect of HPC in terms of heart rate, LVDP, and dp/dtmax (all, p < 0.029).

Conclusions: Rapamycin, through inhibition of mTOR, reduces the elevated HIF-1α expression at an early stage of HPC, and attenuates the early cardioprotective effect of HPC.
keywords:

rapamycin, hypoxic preconditioning, primary neonatal rat cardiomyocytes, hypoxia inducible factor 1α

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