Interaction of hydroxyapatite nanoparticles with endothelial cells: internalization and inhibition of angiogenesis in vitro through the PI3K/Akt pathway

Xingxing Shi,* Kai Zhou,* Fei Huang, Chen Wang Department of Prosthodontics, Jiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: Nano-hydrox...

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Autores principales:	Shi X, Zhou K, Huang F, Wang C
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	HANPs HUVECs internalization angiogenesis PI3K/ Akt Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/560f6b3660124935a8f4de9a1efb8fcc
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spelling	oai:doaj.org-article:560f6b3660124935a8f4de9a1efb8fcc2021-12-02T02:08:25ZInteraction of hydroxyapatite nanoparticles with endothelial cells: internalization and inhibition of angiogenesis in vitro through the PI3K/Akt pathway1178-2013https://doaj.org/article/560f6b3660124935a8f4de9a1efb8fcc2017-08-01T00:00:00Zhttps://www.dovepress.com/interaction-of-hydroxyapatite-nanoparticles-with-endothelial-cells-int-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xingxing Shi,* Kai Zhou,* Fei Huang, Chen Wang Department of Prosthodontics, Jiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: Nano-hydroxyapatite (nano-HAP) has been proposed as a better candidate for bone tissue engineering; however, the interactions of nano-HAP with endothelial cells are currently unclear. In this study, HAP nanoparticles (HANPs; 20 nm np20 and 80 nm np80) and micro-sized HAP particles (m-HAP; 12 µm) were employed to explore and characterize cellular internalization, subcellular distribution, effects of HANPs on endothelial cell function and underlying mechanisms using human umbilical vein endothelial cells (HUVECs) as an in vitro model. It was found that HANPs were able to accumulate in the cytoplasm, and both adhesion and uptake of the HANPs followed a function of time; compared to np80, more np20 had been uptaken at the end of the observation period. HANPs were mainly uptaken via clathrin- and caveolin-mediated endocytosis, while macropinocytosis was the main pathway for m-HAP uptake. Unexpectedly, exposure to HANPs suppressed the angiogenic ability of HUVECs in terms of cell viability, cell cycle, apoptosis response, migration and capillary-like tube formation. Strikingly, HANPs reduced the synthesis of nitric oxide (NO) in HUVECs, which was associated with the inhibition of phosphatidylinositol 3-kinase (PI3K) and phosphorylation of eNOS. These findings provide additional insights into specific biological responses as HANPs interface with endothelial cells. Keywords: HANPs, HUVECs, internalization, angiogenesis, PI3K/Akt Shi XZhou KHuang FWang CDove Medical PressarticleHANPsHUVECsinternalizationangiogenesisPI3K/ AktMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 5781-5795 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	HANPs HUVECs internalization angiogenesis PI3K/ Akt Medicine (General) R5-920
spellingShingle	HANPs HUVECs internalization angiogenesis PI3K/ Akt Medicine (General) R5-920 Shi X Zhou K Huang F Wang C Interaction of hydroxyapatite nanoparticles with endothelial cells: internalization and inhibition of angiogenesis in vitro through the PI3K/Akt pathway
description	Xingxing Shi,* Kai Zhou,* Fei Huang, Chen Wang Department of Prosthodontics, Jiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: Nano-hydroxyapatite (nano-HAP) has been proposed as a better candidate for bone tissue engineering; however, the interactions of nano-HAP with endothelial cells are currently unclear. In this study, HAP nanoparticles (HANPs; 20 nm np20 and 80 nm np80) and micro-sized HAP particles (m-HAP; 12 µm) were employed to explore and characterize cellular internalization, subcellular distribution, effects of HANPs on endothelial cell function and underlying mechanisms using human umbilical vein endothelial cells (HUVECs) as an in vitro model. It was found that HANPs were able to accumulate in the cytoplasm, and both adhesion and uptake of the HANPs followed a function of time; compared to np80, more np20 had been uptaken at the end of the observation period. HANPs were mainly uptaken via clathrin- and caveolin-mediated endocytosis, while macropinocytosis was the main pathway for m-HAP uptake. Unexpectedly, exposure to HANPs suppressed the angiogenic ability of HUVECs in terms of cell viability, cell cycle, apoptosis response, migration and capillary-like tube formation. Strikingly, HANPs reduced the synthesis of nitric oxide (NO) in HUVECs, which was associated with the inhibition of phosphatidylinositol 3-kinase (PI3K) and phosphorylation of eNOS. These findings provide additional insights into specific biological responses as HANPs interface with endothelial cells. Keywords: HANPs, HUVECs, internalization, angiogenesis, PI3K/Akt
format	article
author	Shi X Zhou K Huang F Wang C
author_facet	Shi X Zhou K Huang F Wang C
author_sort	Shi X
title	Interaction of hydroxyapatite nanoparticles with endothelial cells: internalization and inhibition of angiogenesis in vitro through the PI3K/Akt pathway
title_short	Interaction of hydroxyapatite nanoparticles with endothelial cells: internalization and inhibition of angiogenesis in vitro through the PI3K/Akt pathway
title_full	Interaction of hydroxyapatite nanoparticles with endothelial cells: internalization and inhibition of angiogenesis in vitro through the PI3K/Akt pathway
title_fullStr	Interaction of hydroxyapatite nanoparticles with endothelial cells: internalization and inhibition of angiogenesis in vitro through the PI3K/Akt pathway
title_full_unstemmed	Interaction of hydroxyapatite nanoparticles with endothelial cells: internalization and inhibition of angiogenesis in vitro through the PI3K/Akt pathway
title_sort	interaction of hydroxyapatite nanoparticles with endothelial cells: internalization and inhibition of angiogenesis in vitro through the pi3k/akt pathway
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/560f6b3660124935a8f4de9a1efb8fcc
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_version_	1718402648297701376

Interaction of hydroxyapatite nanoparticles with endothelial cells: internalization and inhibition of angiogenesis in vitro through the PI3K/Akt pathway

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