From: Expedition to the missing link: Long noncoding RNAs in cardiovascular diseases
LncRNA | Clinical Relevance | Physiological/pathological impact | Mechanism involved |
---|---|---|---|
H19 [79, 98,99,100] | ↑ in VSMC of neointima and AAA |
EC: Improved wound healing in diabetic rats VSMC: promotes SMC apoptosis and development of AAA |
EC: Hyperglycemia-induced reduction impaired angiogenesis in diabetes through insulin PI3K-Akt pathway VSMC: Regulate VSMC apoptosis through interaction with HIF1α and sequential p53 stabilization |
MALAT1 [81,82,83, 101] | ↑ in VSMC and EC in response to stresses like hypoxia or high glucose |
EC: Deletion delayed vessel extension in the retina revascularization, and reduced blood flow recovery after hindlimb ischemia VSMC: Deletion restores contractile protein gene expression, improves aortic mural architecture, and inhibits experimental aneurysm growth | EC: Inhibit cell cycle progression through reducing the S-phase cyclins while increasing the cell cycle inhibitory genes P21 and P27kip1 |
ANRIL [95, 96] | Adjacent to 9p21.3 CAD risk locus | VSMC: Deleting the risk haplotype rescues VSMC stability | VSMC: regulated cell proliferation and senescence of VSMCs either by a scaffold, guiding effector-proteins to chromatin, or by regulating miR-181a/Sirt1 |
MEG3 [85,86,87] | Downregulated with stroke and diabetic retina | EC: Deletion results in a proangiogenic effect | EC: Deletion upregulate Notch VEGF pathway-related genes |
NEXN-AS1 [88] | Reduced in arterial plaques | NEXN plays a protective role against development of vulnerable atherosclerotic plaques and atherosclerosis | EC: inhibit endothelial activation and monocyte recruitment via the TLR4/NF-κB–mediated pathway |
MANTIS [89, 90] |
Induced by disturbed flow; Reduced in arterial plaques | EC: statins mediate their positive effects through the MANTIS | EC: flow sensitive, limit endothelial ICAM-1 expression by reducing the binding of the BRG1 at the ICAM-1 promoter |
LncLSTR [102] | LncLSTR deletion reduces plasma triglyceride levels by increasing hepatic expression of lipoprotein ApoC2 | Regulate expression of Cyp8b1, which alters the activity of bile acid receptor FXR in liver, leading to induction of ApoC2 genes | |
LeXis [103, 104] | Reduce hepatic cholesterol biosynthesis, serum cholesterol and atherosclerotic lesion | Inhibit cholesterol biosynthesis as a conduit between LXR and SREBP2 | |
MeXis [105] | Deletion in mouse bone marrow cells impairs cellular responses to cholesterol overload, and accelerates atherosclerosis | Modulate nearby gene Abca1 expression through interacting with and guiding promoter binding of the transcriptional coactivator DDX17 |