Table 1.

Non-coding RNAs that stimulate foam cell formation/function.

Non-Coding RNAs	Expression Type	Target Gene	Genetic Information (Human)	Experimental Model		Effect on Foam Cell Formation	Regulation in Lipid Metabolism	Reference
				In Vivo	In Vitro
miR-144-3p		ABCA1	LXR and FXR control miR-144 expression, with both causing an upregulation in this miRNA	ApoE−/− mice	human THP-1 macrophage-derived foam cells	(+) Decrease cholesterol efflux to both apoAI and HDL	decreased HDL-C circulation and impaired RCT in vivo 144-3p mimics (agomir) increases the expression of inflammatory factors such as IL-1b, IL-6 and TNF-α in vivo and in vitro	[103]
miR-33(a/b)		ABCA1, NPC1 ABCG1	encoded within intron 16 of SREBF2, a gene that encodes a key transcriptional regulator of cholesterol uptake and synthesis	miR-33−/− ApoE−/− mice	THP-1 macrophage-derived foam cells	(+) Decrease cholesterol efflux	miR-33 coordinates cholesterol homeostasis	[104,105]
miR-19b		ABCA1	located on chromosome 13q31.3 By an unknown mechanism, expression was increased compared with the control group in advanced human atherosclerotic plaques obtained from patients during endarterectomy	ApoE−/− mice	human THP-1 macrophage-derived foam cells	(+) Decrease the efflux of cholesterol to apoAI	Decrease the levels of HDL (inhibitory role in RCT)	[106]
miR-101		ABCA1	located on chromosome 1p31.3	-	human THP-1-derived macrophages	(+) Decrease the efflux of cholesterol under inflammatory conditions	regulates the availability of free cholesterol for cellular efflux by inhibiting autophagy	[107]
miR-378		ABCG1	The level of miR-378 in the aorta is elevated during the progression of atherosclerosis in apoE−/− mice	ApoE−/− mice	ox-LDL-treated human THP-1 macrophages	(+) Decrease cholesterol efflux	activator protein-1/miRNA-378/ABCG1 is a novel cascade for CoQ10 in facilitating macrophage cholesterol efflux in vitro and in vivo	[108]
miR-302a		ABCA1	located on chromosome 4q25	Ldlr−/− mice	primary human and murine macrophages	(+) Decreases efflux of cholesterol	inhibiting miR-302a in vivo increases ABCA1 in aorta and liver of Ldlr−/− mice and increases circulating HDL	[109]
miR-27		LPL, ACAT1, ABCA1 CD36	located on chromosome 9q22	-	ox-LDL-treated THP-1 macrophages	(+) Reduced cholesterol efflux reduces cholesteryl ester formation blocks lipid uptake	regulates the ratio of cellular free cholesterol (FC) and cholesterol ester (CE) in THP-1 macrophages	[110]
miR-26		ARL7, ABCA1	located on chromosome 3p22.2	-	mouse and human LXR activated macrophages	(+) Downregulate LXR dependent cholesterol efflux	blocks the expression of two important LXR target genes (ABCA1 and ARL7) required for cholesterol efflux	[111]
miR-134		ANGPTL4	located on chromosome 14q32.31	-	THP-1 macrophages	(+) Increase LPL-mediated lipid accumulation	By suppressing the expression of ANGPTL4, which is a regulator of lipoprotein lipase (LPL) activity, it promotes oxLDL uptake and inflammatory responses in vitro	[112]
miR-155		HBP1	located within a region known as the B-cell integration cluster (BIC)	ApoE−/− mice	ox-LDL-treated human THP-1 macrophages	(+) Enhanced lipid uptake and enhanced ROS production	Silencing of miR-155 in ApoE−/− mice by injecting antagomiR-155 decreased the lipid-laden macrophages and the formation of atherosclerotic plaques	[113]
miR-216a		CSE	located on chromosome 2p16.1	-	THP-1 macrophages-derived foam cells	(+) Decreased ABCA1 expression and cholesterol efflux	Downregulation of CSE/H2S leads to an increase in cholesterol accumulation in foam cells	[114]
miR-382-5p		NFIA	located on chromosome 14q32.31	-	THP-1 macrophage-derived foam cells	(+) Reduces cholesterol efflux Increases lipid uptake	RP5-833A20.1/miR-382-5p/NFIA pathway regulates cholesterol homeostasis	[107]
miR-486		HAT1	located on chromosome 8p11.21	-	THP-1 macrophage-derived foam cells	(+) Reduces cholesterol efflux	HAT1 is capable of acetylating H4K5 and H4K12 and increasing ABCA1 expression	[115]
miR-212		SirT1	located on chromosome 17p13.3	ApoE−/− mice	THP-1 human macrophages treated with oxLDL	(+) Suppresses ABCA1 dependent cholesterol efflux	SIRT1 has capable of inducing LXR activity to increase ABCA1 expression in human macrophages	[116]
miR-19a		HBP-1	miR-19a is an important member of the miR-17–92 polycistronic gene cluster MiR-19a is abundant in the blood and tissues of patients with atherosclerotic coronary artery disease	ApoE−/− mice	THP-1 derived macrophages RAW264.7 cells	(+) Increases lipid uptake of macrophages	HBP-1 participates in inhibiting the expression of the macrophage migration inhibitory factor (MIF) and lipid uptake by macrophages size of the atherosclerotic plaques in antagmiR-19a treated mice was reduced	[117]
miR-497		Apelin	Located on chromosome 17q13.1	-	Human THP-1 macrophages treated with oxLDL	(+) Decrease cholesterol efflux to apoA-I.	Apelin is an adipokine that is involved in the pathophysiology of cardiovascular diseases	[118]
miR-20a/b		ABCA1	Mir 20a Located on chromosome 13q31.3 Mir 20b Located on chromosome Xq26.2	ApoE−/− Mice	THP-1 and RAW 264.7 Macrophage-derived foam cells.	(+) Reducing cholesterol Efflux, impairs RCT in vivo	Both in in vitro studies and in ApoE−/− mice treated with miR-20a/b, the hepatic expression of ABCA1, as well as reverse cholesterol transport, are decreased	[119]
miR-758		ABCA1	miR-758 was widely expressed in mouse tissues and particularly abundant in the brain, heart and aorta localized in an intergenic region within chromosome 14	Ldlr−/− mouse	Mouse and human macrophage	(+) Cholesterol efflux to apoA1	effect of miR-758 on cholesterol efflux to ApoA1 was significantly attenuated after ABCA1 silencing decrease in peritoneal macrophages obtained from hypercholesterolemia LDLR−/− mice	[120]
LncRNA MALAT1		CD36, b-catenin	Located on chromosome 11q13.1	-	THP-1-derived macrophage	(+) Enhances lipid uptake	oxLDL induces MALAT1 transcription via the NF-kB pathway Knockdown of MALAT1 using siRNA transfection reduces CD36 expression and affects lipid uptake in macrophages	[121]
LncRNA ENST00000602558.1		ABCG1		-	vascular smooth muscle cells (VSMCs)	(+) Reduce ABCG1-mediated cholesterol efflux to HDL	ENST00000602558.1 induces p65, which is a specific inhibitor of NF-kB and mediates a decrease in the expression of ABCG1	[122]
LncRNA UCA1		Mi R-206	downregulation of UCA1 inhibits oxidative stress and induces apoptosis of THP-1 cells, Located on chromosome 19p13.12	-	THP-1 cells	(+) Increase oxidative stress process In addition, CD36 levels	oxLDL greatly increases UCA1 expression, UCA1 ‘sponges’ miR-206 to exacerbate atherosclerosis	[123]