Phthalate promotes atherosclerosis through interacting with long-non coding RNA and induces macrophage foam cell formation and vascular smooth muscle damage.

Abstract

BACKGROUND:

Phthalates are commonly used in variety of plastic products. Previously it has been revealed that di (2-ethylhexyl) phthalate (DEHP), as the most common member of the class of phthalates, may disturb cholesterol homeostasis and deregulate the inflammatory response, and leading to accelerate the atherosclerosis process. In this regard, the aim of the current study is to explore the underlying mechanism of DEHP-induced atherosclerosis through the increasing of foam cell formation and Vascular Smooth Muscle Cells (VSMCs) damage via the interaction of long-non coding RNA (GAS5) and miR-145-5p.

METHODS:

ApoE-/- mice were used to evaluate the in vivo study. RAW264.7 and VSMCs were used to evaluate the effect of DEHP on formation of foam cell, cell proliferation, and cell damage in vitro. Animals were treated with DEHP (5% w/w of food) orally and cells were treated with medium containing of 100 μM DEHP; qRT-PCR, Western blotting, flowcytometry, IHC, oil red O, BODIPY, and autophagic vacuoles assay were used to evaluate the effect of DEHP on formation of atherosclerosis.

RESULTS:

DEHP significantly accelerated the formation of atherosclerosis in mice and alter the lipid profile in mice. In addition, after treating VSMCs with DEHP, GAS5 was significantly up-regulated and miR-145-5p was down-regulated. In VSMCs treated with DEHP, we observed that GAS5 could be used as the competing endogenous RNA (ceRNA) of miR-145-5p to regulate the proliferation and apoptosis of VSMCs; and the expression of GAS5 was correlated with the expression of miR-145-5p. DEHP increased the ox-LDL uptake by macrophage and increasing the formation of foam cells. Besides, GAS5 knocking down reversed the effect of DEHP on foam cell formation and ox-LDL uptake.

CONCLUSION:

DEHP could accelerate the atherosclerosis process through increasing VSMCs damage and formation of macrophage foam cell by increasing lipid uptake though down regulating lncRNA GAS5 and altering in regulation of miR-145-5p.

• Authors: Chao Liu, Qin Qin, Jinghan Xu, Ximing Li, Hongliang Cong
• Journal: Chemosphere (Chemosphere) Vol. 308 Issue Pt 2 Pg. 136383 (Dec 2022) ISSN: 1879-1298 [Electronic] England
• PMID: 36088979 (Publication Type: Journal Article)
• Copyright: Copyright © 2022. Published by Elsevier Ltd.

Chemical References

• Apolipoproteins E
• Lipoproteins, LDL
• MicroRNAs
• Phthalic Acids
• Plastics
• RNA, Long Noncoding
• phthalic acid
• Cholesterol
• Diethylhexyl Phthalate

Topics

• Animals
• Apolipoproteins E (genetics, metabolism, pharmacology)
• Atherosclerosis (chemically induced, metabolism)
• Cell Movement
• Cell Proliferation
• Cholesterol (metabolism)
• Diethylhexyl Phthalate (metabolism)
• Foam Cells (metabolism)
• Lipoproteins, LDL (metabolism, pharmacology)
• Macrophages (metabolism)
• Mice
• MicroRNAs (metabolism)
• Muscle, Smooth, Vascular (metabolism)
• Phthalic Acids
• Plastics (metabolism)
• RNA, Long Noncoding (genetics, metabolism)