Table 2.

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

Non-Coding RNA	Expression Type	Target Gene	Genetic Information (Human)	Experimental Model		Effect on Foam Cell Formation	Regulation in Lipid Metabolism	Reference
				In Vivo	In Vitro
miR-1275		ApoC2	located on chromosome 6p21.31	-	THP-1 derived macrophages	(−) Inhibited the cellular uptake of Ox-LDL and lipid accumulation	ApoC2 most important cofactor for LPL lipolytic activity	[124]
miR-202-3p		SCARB2, ABCG4, NCEH1I	located on chromosome 10q26.3	-	Human THP-1 macrophage-derived foam cell	(−) Attenuates lipid uptake Enhances cholesterol efflux	Reduces the expression of scavenger receptor SCARB2 Increases the expression of NCEH1 and ABCG4	[125]
miR-181a		TLR4	located on chromosome 1q32.1	-	THP-1	(−) Attenuates lipid uptake and apoptosis and inflammation	Inhibits protein levels of CD36 (scavenger receptor class B)	[126]
miR-135a		TLR4	located on chromosome 3p21.2	-	RAW264.7 and MOVAS cells	(−) Attenuates lipid uptake and inhibit oxidative stress and vascular inflammation	Inhibits CD36 expression	[127]
miR-9		ACAT1	located on chromosome 1q22	-	Human THP-1 macrophage-derived foam cell	(−) Decrease the cholesterol ester formation	Reduces the levels of the ACAT1 protein (Acyl-coenzyme A:cholesterol acyltransferase )	[128]
miR-21		MKK3 MERTK	located on chromosome 17q23.1	Ldlr−/− or miR21−/− mice	Peritoneal macrophages from adult miR21−/− mice	(−) Attenuated cholesterol efflux and promoting the lipid accumulation, Reduce apoptotic cell uptake	Knock down of miR-21 increases the expression of MKK3, promoting the induction of p38-CHOP and jNK signaling, which results in degradation of ABCG1, Decreases expression of MERTK; a key receptor that mediates the clearance of apoptotic cells	[129]
miR-150		AdipoR2	located on chromosome 19q13.33	-	THP-1 macrophages	(−) Attenuates lipid uptake Increases cholesterol efflux	Decreases CD36, upregulates ABCA1 and ABCG1 via the PPARγ- and LXRα-dependent pathways.	[130]
miR-133a		TR4 (testicular orphan nuclear receptor 4)	located on chromosome 18q11.2	-	RAW 264.7 macrophage cells	(−) Decreased oxLDL uptake In addition, lipid accumulation	Decreases expression of CD36	[131]
miR-155		Tim-3, CEH (cholesterol ester hydrolase)	located on chromosome 21q21.3	-	THP-1	(−) Increases cholesterol efflux, Decreased lipid uptake	inhibits Tim-3 expression and increases the expression of CEH resulting in increased expression of ABCA1; inhibits the expression of SR-A,	[132]
miR-155		CARHSP1	located on chromosome 21q21.3	-	THP-1	(−) Decrease inflammation and lipid uptake	suppresses TNF-α production by directly targeting CARHSP1, which is required for TNF-α mRNA stabilization	[133]
miR-98		LOX-1 (Lectin-like ox-LDL scavenger receptor-1)	located on chromosome Xp11.22	ApoE−/− mice	Macrophages were collected from C57BL/6 mice	(−) Decreases the lipid uptake and lipid accumulation	decreases LOX-1 expression	[134]
miR-223		TLR4-NF-κB signaling pathway	located on chromosome Xq12	ApoE−/− mouse, C57BL/6J wild-type mice(control)	Murine macrophage cell line RAW 264.7	(−) Increase cholesterol efflux to apoA-I, Decrease inflammation	activates the PI3K/AKT signaling pathway	[135]
miR-23a		HSP90	located on chromosome 19p13.12	-	THP-1 macrophages	(−) Inhibit lipid accumulation	Decreased apoptosis of foam cells; decreases inflammation factors by inhibiting the activation of NF-κB pathways	[136]
miR-146b-5p		TRAF6	located on chromosome 10q24.32	-	THP-1 human monocytic and the HEK293T human embryonic kidney cell line	(−) Decrease lipid uptake	miR-146-5p inhibitor increases TRAF6-mediated activation of NF-κB (p65) and increases inflammatory response	[137]
miR-221-3p		ADAM22	located on chromosome Xp11.3	-	RAW264.7	(−) Decrease lipid uptake	Decreases CD36; decrease oxidative stress and apoptosis	[138]
miR-16		PDCD4 (Programmed cell death 4)	located on chromosome 13q14	ApoE−/− mice	macrophage-derived foam cell (RAW264.7)	(−)	Suppresses the activation of inflammatory macrophages and decreases release of inflammatory cytokines via the MAPK and NF-κB pathways	[139]
miR-34a		HDAC1 (histone deacetylase 1)	located on chromosome 1p36.22	Male C57BL/6J and ApoE−/− mice	Human THP-1 macrophages	(−) Prevents the accumulation of triglyceride and total and free cholesterol	Hyperhomocysteinemia (HHcy) accelerates atherogenesis via decreased expression of miR-34a	[140]
Let-7g		NF-κB complex MEKK1	located on chromosome 3p21.2	ApoE−/− mouse, IKKαf/f:MLysCre/apoE−/− mice	Human THP-1 macrophage	(−) increase cholesterol efflux, Decrease intracellular lipid accumulation	up-regulates SREBF2, which is a critical regulator of cholesterol/lipid homeostasis, up-regulates ABCA1 via suppression of miR-33a, decreases p53-dependent apoptosis	[141]
LncRNA CDKN2B-AS1		ADAM10	located on chromosome 9p21.3	ApoE−/− Mice, C57BL/6J Mice	THP-1 macrophage-derived foam cells	(−) Increases Cholesterol Efflux, Decrease lipid accumulation	Inhibits inflammatory responses by suppressing the transcription of ADAM10	[142]
LncRNA DYNLRB2-2		miR-298	located on chromosome 16q23.2	-	THP-1 macrophage-derived foam cells	(−) Impairing oxLDL uptake, increases cholesterol efflux	Induces autophagy by activating the LKB1/AMPK/mTOR signaling pathway via the miR-298/SIRT3 axis; decreases the expression of TLR2 and enhances the expression of ABCA1	[143]