LncRNA MALAT1 Enhances ox-LDL-Induced Autophagy through the SIRT1/MAPK/NF-κB Pathway in Macrophages

Abstract

Aims: We aimed to detected the biological function of LncRNA MALAT1 in regulating macrophage-related autophagy. Background: Atherosclerosis is the mainly cause of cardiovascular and cerebrovascular diseases, which lead to the second cause of death worldwide. In advanced atherosclerotic plaque, macrophage apoptosis coupled with inflammatory cytokines secretion promotes the formation of necrotic cores. Objective: To demonstrate the MALAT1-related autophagy and find related signaling pathway. Method: We utilized ox-LDL to incubate THP-1-derived macrophages in order to establish the foam cell model in vitro. RT-qPCR and western blot analyses confirmed the increasing expression level of MALAT1 and autophagy-related protein LC-3, Beclin-1. Si-RNAs study showed the significant decrease in autophagy activity and increase in apoptotic rate when knocking down MALAT1. Further study demonstrated that MALAT1 inhibited the expression of MAPK and NF-κB (p65) by up-regulating SIRT1. Result: Here we demonstrated that the long non-coding RNA MALAT1, which has attracted increasingly attention by its potent function on gene transcription modulation, is also indispensable for maintaining oxidized low density lipoproteins (ox-LDL)-induced autophagy in macrophage. Besides, we also proved that MALAT1 exerted its protective function by activating SIRT1, which subsequently inhibit the MAPK and NF-κB signaling pathway. Conclusion: LncRNA MALAT1 Enhances Ox-LDL-induced Autophagy via the SIRT1/MAPK/NF-κB Pathway in Macrophages.

Small interfering RNA-induced silencing lncRNA PVT1 inhibits atherosclerosis via inactivating the MAPK/NF-κB pathway

“…PVT1 was upregulated in the myocardial tissues of sepsis rats, activated the MAPK/NF-κB pathway, and thus inhibited cardiac function and promoted the secretion of inflammatory factors [ 18 ]. A previous study verified that another lncRNA, MALAT1 enhances ox LDL-induced autophagy of macrophages in AS by diminishing the expressions of MAPK and NF-κB in AS [ 39 ]. We finally came to a conclusion that the protective role of siRNA induced lncRNA PVT1 suppression in AS was achieved via the downregulation of MAPK/NF-κB pathway.…”

The sirtuin family in health and disease

“…For instance, lncRNA metastasis-associated lung adenocarcinoma transcript 1 enhances ox- low-density lipoprotein (LDL)-induced autophagy through the SIRT1/MAPK/NF-κB pathway. 295 lncRNA growth arrest specific 5 inhibits macroautophagy and forms a negative feedback regulatory loop with the miR-34a/SIRT1/mammalian target of rapamycin (mTOR) pathway. 296 In conclusion, SIRT1 is a key regulator of the autophagic process.…”

IRGM/Irgm1 Aggravates Progression of Atherosclerosis by Inducing Macrophage Apoptosis through the MAPK Signaling Pathway

“…Much evidence has accrued that the apoptosis of macrophages can influence the stability of atherosclerotic plaques (25,47). Macrophage apoptosis intensifies the formation of plaque necrotic cores, causes thinning of the fibrous cap, and ultimately leads to PR (48)(49)(50). Therefore, we speculate that IRGM/Irgm1 contributes to plaque vulnerability by promoting macrophage apoptosis in advanced atherosclerotic plaques.…”

“…Evidence has amassed that macrophage apoptosis intensifies formation of plaque necrotic cores, causing thinning of the fibrous cap, and ultimately leading to PR (25, 47) (48–50). In this study, we first explored the effect of Irgm1 on atherosclerotic plaque phenotype in mice.…”