Nano-hydroxyapatite accelerates vascular calcification via lysosome impairment and autophagy dysfunction in smooth muscle cells

Vascular calcification (VC) is a common characteristic of aging, diabetes, chronic renal failure, and atherosclerosis. The basic component of VC is hydroxyapatite (HAp). Nano-sized HAp (nHAp) has been identified to play an essential role in the development of pathological calcification of vasculatur...

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Autores principales:	Qi Liu, Yi Luo, Yun Zhao, Pingping Xiang, Jinyun Zhu, Wangwei Jing, Wenjing Jin, Mingyao Chen, Ruikang Tang, Hong Yu
Formato:	article
Lenguaje:	EN
Publicado:	KeAi Communications Co., Ltd. 2022
Materias:	Nano-hydroxyapatite Vascular calcification Autophagy Lysosome Exosome Materials of engineering and construction. Mechanics of materials TA401-492 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b96630a5c0ae41f7af9cee6b1831fc55
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spelling	oai:doaj.org-article:b96630a5c0ae41f7af9cee6b1831fc552021-11-04T04:34:56ZNano-hydroxyapatite accelerates vascular calcification via lysosome impairment and autophagy dysfunction in smooth muscle cells2452-199X10.1016/j.bioactmat.2021.06.004https://doaj.org/article/b96630a5c0ae41f7af9cee6b1831fc552022-02-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2452199X21002875https://doaj.org/toc/2452-199XVascular calcification (VC) is a common characteristic of aging, diabetes, chronic renal failure, and atherosclerosis. The basic component of VC is hydroxyapatite (HAp). Nano-sized HAp (nHAp) has been identified to play an essential role in the development of pathological calcification of vasculature. However, whether nHAp can induce calcification in vivo and the mechanism of nHAp in the progression of VC remains unclear. We discovered that nHAp existed both in vascular smooth muscle cells (VSMCs) and their extracellular matrix (ECM) in the calcified arteries from patients. Synthetic nHAp had similar morphological and chemical properties as natural nHAp recovered from calcified artery. nHAp stimulated osteogenic differentiation and accelerated mineralization of VSMCs in vitro. Synthetic nHAp could also directly induce VC in vivo. Mechanistically, nHAp was internalized into lysosome, which impaired lysosome vacuolar H+-ATPase for its acidification, therefore blocked autophagic flux in VSMCs. Lysosomal re-acidification by cyclic-3′,5′-adenosine monophosphate (cAMP) significantly enhanced autophagic degradation and attenuated nHAp-induced calcification. The accumulated autophagosomes and autolysosomes were converted into calcium-containing exosomes which were secreted into ECM and accelerated vascular calcium deposit. Inhibition of exosome release in VSMCs decreased calcium deposition. Altogether, our results demonstrated a repressive effect of nHAp on lysosomal acidification, which inhibited autophagic degradation and promoted a conversion of the accumulated autophagic vacuoles into exosomes that were loaded with undissolved nHAp, Ca2+, Pi and ALP. These exosomes bud off the plasma membrane, deposit within ECM, and form calcium nodules. Vascular calcification was thus accelerated by nHAP through blockage of autophagic flux in VSMCs.Qi LiuYi LuoYun ZhaoPingping XiangJinyun ZhuWangwei JingWenjing JinMingyao ChenRuikang TangHong YuKeAi Communications Co., Ltd.articleNano-hydroxyapatiteVascular calcificationAutophagyLysosomeExosomeMaterials of engineering and construction. Mechanics of materialsTA401-492Biology (General)QH301-705.5ENBioactive Materials, Vol 8, Iss , Pp 478-493 (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Nano-hydroxyapatite Vascular calcification Autophagy Lysosome Exosome Materials of engineering and construction. Mechanics of materials TA401-492 Biology (General) QH301-705.5
spellingShingle	Nano-hydroxyapatite Vascular calcification Autophagy Lysosome Exosome Materials of engineering and construction. Mechanics of materials TA401-492 Biology (General) QH301-705.5 Qi Liu Yi Luo Yun Zhao Pingping Xiang Jinyun Zhu Wangwei Jing Wenjing Jin Mingyao Chen Ruikang Tang Hong Yu Nano-hydroxyapatite accelerates vascular calcification via lysosome impairment and autophagy dysfunction in smooth muscle cells
description	Vascular calcification (VC) is a common characteristic of aging, diabetes, chronic renal failure, and atherosclerosis. The basic component of VC is hydroxyapatite (HAp). Nano-sized HAp (nHAp) has been identified to play an essential role in the development of pathological calcification of vasculature. However, whether nHAp can induce calcification in vivo and the mechanism of nHAp in the progression of VC remains unclear. We discovered that nHAp existed both in vascular smooth muscle cells (VSMCs) and their extracellular matrix (ECM) in the calcified arteries from patients. Synthetic nHAp had similar morphological and chemical properties as natural nHAp recovered from calcified artery. nHAp stimulated osteogenic differentiation and accelerated mineralization of VSMCs in vitro. Synthetic nHAp could also directly induce VC in vivo. Mechanistically, nHAp was internalized into lysosome, which impaired lysosome vacuolar H+-ATPase for its acidification, therefore blocked autophagic flux in VSMCs. Lysosomal re-acidification by cyclic-3′,5′-adenosine monophosphate (cAMP) significantly enhanced autophagic degradation and attenuated nHAp-induced calcification. The accumulated autophagosomes and autolysosomes were converted into calcium-containing exosomes which were secreted into ECM and accelerated vascular calcium deposit. Inhibition of exosome release in VSMCs decreased calcium deposition. Altogether, our results demonstrated a repressive effect of nHAp on lysosomal acidification, which inhibited autophagic degradation and promoted a conversion of the accumulated autophagic vacuoles into exosomes that were loaded with undissolved nHAp, Ca2+, Pi and ALP. These exosomes bud off the plasma membrane, deposit within ECM, and form calcium nodules. Vascular calcification was thus accelerated by nHAP through blockage of autophagic flux in VSMCs.
format	article
author	Qi Liu Yi Luo Yun Zhao Pingping Xiang Jinyun Zhu Wangwei Jing Wenjing Jin Mingyao Chen Ruikang Tang Hong Yu
author_facet	Qi Liu Yi Luo Yun Zhao Pingping Xiang Jinyun Zhu Wangwei Jing Wenjing Jin Mingyao Chen Ruikang Tang Hong Yu
author_sort	Qi Liu
title	Nano-hydroxyapatite accelerates vascular calcification via lysosome impairment and autophagy dysfunction in smooth muscle cells
title_short	Nano-hydroxyapatite accelerates vascular calcification via lysosome impairment and autophagy dysfunction in smooth muscle cells
title_full	Nano-hydroxyapatite accelerates vascular calcification via lysosome impairment and autophagy dysfunction in smooth muscle cells
title_fullStr	Nano-hydroxyapatite accelerates vascular calcification via lysosome impairment and autophagy dysfunction in smooth muscle cells
title_full_unstemmed	Nano-hydroxyapatite accelerates vascular calcification via lysosome impairment and autophagy dysfunction in smooth muscle cells
title_sort	nano-hydroxyapatite accelerates vascular calcification via lysosome impairment and autophagy dysfunction in smooth muscle cells
publisher	KeAi Communications Co., Ltd.
publishDate	2022
url	https://doaj.org/article/b96630a5c0ae41f7af9cee6b1831fc55
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Nano-hydroxyapatite accelerates vascular calcification via lysosome impairment and autophagy dysfunction in smooth muscle cells

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