Table 1.
LncRNAs in atherosclerosis
| LncRNA | Binding partner | Function | Ref | |||
|---|---|---|---|---|---|---|
| Human specimen | In vivo | In vitro | ||||
| LASER | Lipid Associated Single nucleotide polymorphism gEne Region | lncRNA-protein | Positively correlated with cholesterol levels in PBMC patients | N/A | Deficiency: ↓ cholesterol in HepG2 cells, further reduced with statin treatment | 31 |
| LeXis | Liver-expressed LXR-induced sequence | lncRNA-protein | N/A | Overexpression: C57BL/6 mice, AV LeXis ↓circulating and hepatic cholesterol content Deficiency: C57BL/6 mice, LeXIS ASO ↑ cholesterogenic gene expression ↑ serum levels | N/A | 32 |
| MeXis | Macrophage-expressed LXR-induced sequence | lncRNA-protein | N/A | Deficiency:Ldlr−/− on WD + MeXis−/− bone marrow↓ Abca1 expression ↑ inflammatory gene expression ↑ lesion size ↑ CD68+ cells | Deficiency: Peritoneal macrophages (MeXis−/− mice fed aWD) ↓ ABCA1 ↓ cholesterol efflux ↑ cholesterol accumulation | 35 |
| ANRIL; CDKN2B-AS1 | Antisense non coding RNA in the INK4 locus | lncRNA-protein | ↓ atherosclerotic plaque | Overexpression: ApoE−/− on HFD, LV-induced OE ↑ Cholesterol efflux ↓ lesion size ↓ inflammation | Overexpression: THP-1 (oxLDL) ↑ cholesterol efflux ↓ lipid accumulation ↓ inflammation ↓ ADAM10 | 36, 37 |
| NEXN-AS1 | Nexilin F-actin binding protein antisense RNA 1 | lncRNA-protein | ↓ atherosclerotic plaques ↓ NEXN in CAD patients (blood) | Deficiency: NEXN± /ApoE−/− on WD ↑ lesion area, macrophage abundance, expression of adhesion molecules ↑ inflammatory cytokines | Overexpression: HUVECs ↓ TLR4/NF-kB pathway ↓ inflammatory gene expression | 40, 41 |
| MANTIS | lncRNA-protein | ↓ atherosclerotic plaque | Deficiency: Retinal injection of siRNA MANTIS ↑ ICAM-1 | Deficiency: HUVECs ↓ angiogenic genes ↑ ICAM-1 ↑ monocyte adhesion ↑ apoptosis ↑ oxidative stress | 42, 43 | |
| LncRNA-CCL2 | C-C Motif Chemokine Ligand 2 | lncRNA-protein | ↑ unstable symptomatic atherosclerotic plaque | N/A | Deficiency: HUVEC (IL-1ß) ↓ CCL2 | 44 |
| NEAT1 | Nuclear paraspeckle assembly transcript 1 | lncRNA-protein | N/A | Deficiency: NEAT1± , Carotid Artery Ligation Injury ↓ VSMC proliferation and migration ↓ Neointima formation | Overexpression: ↑ VSMC proliferation and migration Deficiency:↓ VSMC proliferation and migration | 46 |
| SNHG12 | Small nucleolar host gene-12 | lncRNA-protein | Inverse correlation of SNHG12 expression with DNA damage and senescence markers in human atherosclerosis | Overexpression:ApoE−/− mice on HCD ↓ lesion area ↓ lipid accumulation ↓ DNA damage (yH2AX) Deficiency: Ldlr−/− on HCD, gapmeR-induced KO ↑ lesion area ↑ lipid accumulation ↑ plaque necrosis ↓ efferocytosis ↑ DNA damage (yH2AX) | Deficiency HUVEC ↑ yH2AX ↑ tail moment | 47 |
| FA2H-2 | Fatty Acid 2-Hydroxylase 2 | lncRNA-DNA | ↓ atherosclerotic plaque | Deficiency: ApoE−/− + LV-si-lncRNA-FA2H-2 on WD ↑ autophagy flux ↑ inflammatory response ↑ increased lesion area | Deficiency: ECs and SMCs (oxLDL) ↑ autophagy flux ↑ increased inflammatory response | 49 |
| SMILR | Smooth muscle–induced lncRNA enhances replication | lncRNA-RNA | ↑ unstable atherosclerotic plaque ↑in plasma from patients with high plasma C-reactive protein | N/A | Deficiency: ↑ Proliferation of arterial and venous SMCs | 55, 56 |
| CHROME | Cholesterol Homeostasis Regulator of MiRNA Expression | lncRNA-RNA | ↑ CAD (plasma), ↑ symptomatic versus asymptomatic atherosclerotic plaques | N/A | Deficiency: HepG2 cells, primary human hepatocytes, THP-1 ↓ ABCA1 protein expression ↓ cholesterol efflux to exogenous apoA-1 | 57 |
| RP5-833A20.1 | lncRNA-RNA | N/A | Overexpression: ApoE−/− on HFD, LV-induced NFIA OE ↑ cholesterol efflux ↓ lesion size ↓ lipid accumulation | Overexpression: THP-1 (oxLDL) ↓ cholesterol efflux ↑ lipid accumulation ↑ miR-382-5p ↓ NFIA | 58 | |
| DAPK1-IT1 | DAPK1 Intronic Transcript 1 | lncRNA-RNA | N/A | Overexpression: ApoE−/− on HFD, LV-induced LPL OE ↓ HDL-C, ↑ LDL-C ↑ circulating proinflammatory cytokines ↑ lesion size, ↑ lipid accumulation ↓ ABCA1 | Overexpression: THP-1 (oxLDL) ↓ miR5903p ↑ LPL (same for def), ↑ total CH ↓ cholesterol efflux ↑ inflammatory cytokines Deficiency: THP-1 (oxLDL) ↑ miR5903p ↓ LPL | 59 |
| GAS5 | Growth-arrest Specific 5 | lncRNA-protein lncRNA-RNA | N/A | Overexpression: ApoE−/− on HFD, LV-induced OE ↓ HDL-C, ↑ LDL-C ↓ reduced cholesterol efflux ↑ lesion size ↑ inflammation Deficiency: ApoE−/− on HFD, sh-GAS5 ↑HDL-C, ↓ LDL-C ↑ reduced cholesterol efflux ↓ lesion size ↓ inflammation | Overexpression: THP-1 (oxLDL) ↓ cholesterol efflux ↑ lipid accumulation ↓ ABCA1 ↑ inflammatory markers ↑ MMP-2, MMP-9 ↑ EZH ↓ miR-135 ↓ miR-221 Deficiency: THP-1 (oxLDL) ↑ cholesterol efflux ↓ lipid accumulation ↑ABCA1 ↓ inflammatory markers ↓ MMP- | 38, 60–63 |
| MALAT1 | Metastasis-associated lung adenocarcinoma transcript 1 | lncRNA-RNA | ↓ atherosclerotic plaque, correlates with symptoms of plaque instability | Deficiency: ApoE−/− Malat1−/− bone marrow cells on HFD ↑ adhesion to endothelial cells ↑ proinflammatory mediators ↑ lesion size ↑ miR-503 | Deficiency: HUVECs (oxLDL) ↓ autophagy ↑ apoptosis ↑ miR-216a-5p EA.hy926 cells (high glucose) ↓ pryoptosis ↓ NLRP3 ↑ miR-22 | 64–68 |
| MEG3 | Maternally Expressed 3 | lncRNA-RNA | N/A | Overexpression: Ldlr−/− on HFD ↓ CD68+, CD3+, ICAM-1 ↑ collagen content | Overexpression: HMEC-1 ↓ cell viability, migration, tube formation ↑apoptosis suppress miR-147 Deficiency: VSMCs ↑ proliferation ↓ apoptosis ↓ ABCA1 suppress miR-361-5p | 71, 72 |
| CERNA1 | Competing Endogenous lncRNA 1 For MiR-4707-5p And MiR-4767 | lncRNA-RNA | N/A | Overexpression: ApoE−/− on HFD, LV-induced OE ↑ VSMCs ↓ IL-6 ↓ necrotic core area ↓ apoptosis | Overexpression: HUVEC (oxLDL) ↓ apoptosis ↓miR4707-5p Deficiency: HUVEC (oxLDL) ↑ apoptosis ↑miR4707-5p | 73, 74 |
| MIAT | Myocardial infarction associated transcript | lncRNA-RNA | ↑ serum of patients with symptomatic atherosclerotic disease | Deficiency: ApoE−/− on HFD, shRNA-induced KD ↓ lesion size ↓ necrotic core ↑ fibrous cap ↑ collagen ↑ efferocytosis | Deficiency: BMDM (oxLDL) ↑ phagocytosis Raw264.7 (oxLDL) ↑ miR-149-5p ↓ CD47 | 75 |
| TUG1 | Taurine upregulated gene 1 | lncRNA-RNA | N/A | Deficiency: ApoE−/− on HFD, siRNA-induced KD ↓ hyperlipidemia ↓ inflammatory response ↓ lesion size | Overexpression: RAW264.7 (oxLDL) ↑ cell growth ↓ apoptosis ↑ inflammation ↓ miR-133a Deficiency: VSMCs (oxLDL) ↓ proliferation ↑ apoptosis ↓ miR148b HUVECs (oxLDL) ↑ proliferation ↓ apoptosis ↓ miR148b | 76, 77 |
| HOXA-AS2 | HOXA Cluster Antisense RNA 2 | N/A | ↑ atherosclerotic lesions | N/A | Deficiency: HUVECs ↑ NF-kB signaling, ↑ inflammatory response | 78 |
| PELATON | Plaque enriched lncRNA in atherosclerotic and inflammatory bowel macrophage regulation | N/A | ↑ unstable atherosclerotic plaque | N/A | Deficiency: CD14+ hdPBMC ↓ phagocytosis ↓ oxLDL uptake ↓CD36 | 79 |