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Hepatocyte growth factor protects endothelial progenitor cell from damage of low-density lipoprotein cholesterol via the PI3K/Akt signaling pathway

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Abstract

Risk factors for coronary heart disease including low-density lipoprotein (LDL) cholesterol can reduce the number and activity of endothelial progenitor cells (EPCs), thereby hindering their usefulness for treating cardiovascular disease in transplants. The aim of this study was to investigate whether hepatocyte growth factor (HGF) can protect EPCs from the inhibition caused by LDL cholesterol. EPCs derived from mouse bone marrow were isolated and cultured in medium supplemented with different concentrations of LDL cholesterol. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, modified Boyden chambers and flow cytometry were used to evaluate EPC proliferation, migration and apoptosis. The role of Akt in this process was also evaluated through observing the expressions of total Akt and Akt phosphorylation, and pharmacological analysis. Our results indicate that LDL cholesterol inhibits the proliferation and migration of EPCs, and induces their apoptosis. However, HGF improves the activity of EPCs inhibited by LDL cholesterol, and it simultaneously decreases EPC apoptosis induced by LDL cholesterol. Blockade of phosphoinositide-3 kinase (PI3K) by Ly294002 attenuates the effect of HGF. Furthermore, our experiments suggest that HGF increases the level of phosphorylated Akt in EPCs rather than Akt. However, PI3K inhibitor reduces the increase of phosphorylated Akt level induced by HGF. These findings suggest HGF promotes endothelial progenitor cells migration, proliferation and survival impaired by low-density lipoprotein cholesterol via the PI3K/Akt signaling pathway.

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Acknowledgments

The study is supported by grants from the National Natural Science Foundation of China (No. 30570765 and No. 30700889) and the Natural Science Foundation of Chongqing, China (No. CSTC, 2005bb5304).

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Authors and Affiliations

  1. Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Third Military Medical University, 400037, Chongqing, People’s Republic of China

    XueJun Yu, MingBao Song, JianFei Chen, Gang Zhao & Lan Hunag

  2. Department of Clinical Laboratory, Kunming General Hospital, Chengdu Military Area of PLA, 650032, Kunming, People’s Republic of China

    GuangXu Zhu & Hong Wang

Authors
  1. XueJun Yu
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  2. MingBao Song
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  3. JianFei Chen
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  4. GuangXu Zhu
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  5. Gang Zhao
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  6. Hong Wang
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  7. Lan Hunag
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Correspondence to Lan Hunag.

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XueJun Yu and MingBao Song contributed equally to this work.

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Yu, X., Song, M., Chen, J. et al. Hepatocyte growth factor protects endothelial progenitor cell from damage of low-density lipoprotein cholesterol via the PI3K/Akt signaling pathway. Mol Biol Rep 37, 2423–2429 (2010). https://doi.org/10.1007/s11033-009-9753-6

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  • DOI: https://doi.org/10.1007/s11033-009-9753-6

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