The promotion effect of novel magnetic nanoparticles on atherosclerotic plaque vulnerability in apolipoprotein E-/- mice

Guojing Qu; Qinghua Wu; Baoxiang Zhao; Junying Miao; Le Su

doi:10.1016/j.tox.2019.03.002

The promotion effect of novel magnetic nanoparticles on atherosclerotic plaque vulnerability in apolipoprotein E^-/- mice

Toxicology. 2019 May 1:419:24-31. doi: 10.1016/j.tox.2019.03.002. Epub 2019 Mar 18.

Authors

Guojing Qu¹, Qinghua Wu¹, Baoxiang Zhao², Junying Miao¹, Le Su³

Affiliations

¹ Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, China.
² Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, China.
³ State Key Laboratory of Biobased Material and Green Papermaking, School of bioengineering, Qilu University of Technology, Shandong Academy of Sciences, Jinan, 250353, China; Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, China. Electronic address: sule@sdu.edu.cn.

PMID: 30898670
DOI: 10.1016/j.tox.2019.03.002

Abstract

Although manufactured magnetic nanoparticles (NPs) are currently used in many fields, NPs have potential toxicity on cardiovascular system especially atherosclerosis. In our previous study, we prepared novel Fe₃O₄ nanoparticles surface-coated with aminoguanidine (Fe₃O₄-AG NPs) which could remove acid dyes from aqueous solution efficiently. To understand its biocompatibility to atherosclerotic plaque vulnerability, we investigated the effects of the nanoparticles on human umbilical vein endothelial cells (HUVECs) in vitro and plaque stability in vivo. Fe₃O₄-AG NPs were taken up by HUVECs and induced HUVEC apoptosis. Fe₃O₄-AG NP injection remarkably promoted plaque vulnerability at low-dose (0.5 mg/kg) but not high-dose (5.0 mg/kg) in apolipoprotein E^-/- (ApoE^-/-) mice. Further study indicated that Fe₃O₄-AG NP-induced atherosclerotic plaque vulnerability was tightly linked to bioactivity of nitric oxide (NO). A significant decrease in NO production was induced which coincided with the inhibition of endothelial nitric oxide synthase (eNOS) activity in serum and endothelium of plaque in ApoE^-/- mice injected with low-dose Fe₃O₄-AG NPs in vivo and HUVECs treated with low-dose Fe₃O₄-AG NPs in vitro. Thus, the low concentration of Fe₃O₄-AG NPs presented toxicity to atherosclerosis. Our results indicated that the use of Fe₃O₄-AG NPs to improve aqueous solution pollution should be cautious due to the potential toxicity.

Keywords: NO; Plaque vulnerability; Vascular endothelial cells; agnetic nanoparticles; eNOS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Aorta / drug effects*
Aorta / metabolism
Aorta / pathology
Aortic Diseases / chemically induced*
Aortic Diseases / genetics
Aortic Diseases / metabolism
Aortic Diseases / pathology
Apoptosis / drug effects
Atherosclerosis / chemically induced*
Atherosclerosis / genetics
Atherosclerosis / metabolism
Atherosclerosis / pathology
Cells, Cultured
Disease Models, Animal
Guanidines / toxicity*
Human Umbilical Vein Endothelial Cells / drug effects
Human Umbilical Vein Endothelial Cells / pathology
Humans
Magnetite Nanoparticles / toxicity*
Male
Mice, Inbred C57BL
Mice, Knockout, ApoE
Nitric Oxide / metabolism
Nitric Oxide Synthase Type III / metabolism
Plaque, Atherosclerotic*
Rupture, Spontaneous

Substances

Guanidines
Magnetite Nanoparticles
Nitric Oxide
NOS3 protein, human
Nitric Oxide Synthase Type III
Nos3 protein, mouse
pimagedine