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Apolipoprotein A-I mimetic peptide D-4F promotes human endothelial progenitor cell proliferation, migration, adhesion though eNOS/NO pathway

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Abstract

Circulating endothelial progenitor cells (EPCs) have a critical role in endothelial maintenance and repair. Apolipoprotein A-I mimetic peptide D-4F has been shown to posses anti-atherogenic properties via sequestration of oxidized phospholipids, induction of remodeling of high density lipoprotein and promotion of cholesterol efflux from macrophage-derived foam cells. In this study, we test the effects of D-4F on EPC biology. EPCs were isolated from the peripheral venous blood of healthy male volunteers and characterized by 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine-labeled acetylated LDL uptake and ulex europaeus agglutinin binding and flow cytometry. Cell proliferation, migration, adhesion, nitric oxide production and endothelial nitric oxide synthase (eNOS) expression in the absence and presence of D-4F or simvastatin (as a positive control), were assayed. We demonstrated that D-4F significantly enhanced EPC proliferation, migration and adhesion in a dose-dependent manner compared with vehicle. However, all of the favorable effects of D-4F on EPCs were dramatically attenuated by preincubation with NOS inhibitor L-NAME. Further, D-4F also increased nitric oxide production in culture supernatant and the levels of eNOS expression and phosphorylation. The stimulatory effects of D-4F (10 μg/ml) on EPC biology were comparable to 0.5 μM simvastatin. These results suggest that eNOS/NO pathway mediates the functional modulation of EPC biology in response to D-4F treatment and support the notion that the beneficial role of D-4F on EPCs may be one of the important components of its anti-atherogenic potential.

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Acknowledgments

We appreciate Dr. Baran Aksut for the revision of the manuscript. This work was supported by the Basic Research Project (Natural Science Foundation) of Jiangsu Province (BK2008220, BK2010324) and the National Natural Science Foundation of China (81070096).

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Authors and Affiliations

  1. Department of Cardiology, The Second Clinic Medical College, Yangzhou University, Yangzhou, 225001, China

    Zhengang Zhang, Jianhua Qun, Chunmei Cao, Jun Wang, Wei Li, Yong Wu, Lin Du, Pei Zhao & Kaizheng Gong

  2. Institute of Cardiovascular Disease (Yangzhou), Southeast University, Yangzhou, 225001, China

    Zhengang Zhang

  3. No. 45 Taizhou Road, Yangzhou, 225001, China

    Kaizheng Gong

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  1. Zhengang Zhang
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  2. Jianhua Qun
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Correspondence to Kaizheng Gong.

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Zhengang Zhang and Jianhua Qun authors contributed equally to this study.

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Zhang, Z., Qun, J., Cao, C. et al. Apolipoprotein A-I mimetic peptide D-4F promotes human endothelial progenitor cell proliferation, migration, adhesion though eNOS/NO pathway. Mol Biol Rep 39, 4445–4454 (2012). https://doi.org/10.1007/s11033-011-1233-0

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