Autophagic Marker MAP1LC3B Expression Levels Are Associated with Carotid Atherosclerosis Symptomatology

Abstract

ObjectivesThe mechanism by which atheroma plaque becomes unstable is not completely understood to date but analysis of differentially expressed genes in stable versus unstable plaques may provide clues. This will be crucial toward disclosing the mechanistic basis of plaque instability, and may help to identify prognostic biomarkers for ischaemic events. The objective of our study was to identify differences in expression levels of 59 selected genes between symptomatic patients (unstable plaques) and asymptomatic patients (stable plaques).Methods80 carotid plaques obtained by carotid endarterectomy and classified as symptomatic (>70% stenosis) or asymptomatic (>80% stenosis) were used in this study. The expression levels of 59 genes were quantified by qPCR on RNA extracted from the carotid plaques obtained by endarterectomy and analyzed by means of various bioinformatic tools.ResultsSeveral genes associated with autophagy pathways displayed differential expression levels between asymptomatic and symptomatic (i.e. MAP1LC3B, RAB24, EVA1A). In particular, mRNA levels of MAP1LC3B, an autophagic marker, showed a 5−fold decrease in symptomatic samples, which was confirmed in protein blots. Immune system−related factors and endoplasmic reticulum-associated markers (i.e. ERP27, ITPR1, ERO1LB, TIMP1, IL12B) emerged as differently expressed genes between asymptomatic and symptomatic patients.ConclusionsCarotid atherosclerotic plaques in which MAP1LC3B is underexpressed would not be able to benefit from MAP1LC3B−associated autophagy. This may lead to accumulation of dead cells at lesion site with subsequent plaque destabilization leading to cerebrovascular events. Identified biomarkers and network interactions may represent novel targets for development of treatments against plaque destabilization and thus for the prevention of cerebrovascular events.

A Locus at 5q33.3 Confers Resistance to Tuberculosis in Highly Susceptible Individuals

“…50 Importantly, these SNPs are also in proximity to IL12B, a gene previously associated with both TB 9,51 and leprosy. 52 IL12B variants have also been associated with carotid stenosis 53 and psoriasis, 54 possibly owing to LD with SNPs in UBLCP1. IL12B encodes p40, one of two subunits of interleukin-12 (IL-12) 55 and IL-23.…”

Mitophagy in Cardiovascular Diseases

“…In the last 10 years, various methods have been applied to assess autophagy in cells that form atherosclerotic plaques (VSMCs, endothelial cells, macrophages), including electron microscopy, fluorescence microscopy and western blot approaches [44,45]. Studies conducted on human specimens and mouse models of AS have reported either dysfunctional or decreased autophagy based on detection of the autophagic markers p62 and LC3-II in cells isolated from plaques [46][47][48]. Indeed, a strong decrease in LC3-II expression has been reported in patients with unstable plaques compared to those with stable plaques [48]; such decreases would enable dead cell accumulation in the artery wall and subsequent plaque destabilization ( Figure 2).…”

“…Studies conducted on human specimens and mouse models of AS have reported either dysfunctional or decreased autophagy based on detection of the autophagic markers p62 and LC3-II in cells isolated from plaques [46][47][48]. Indeed, a strong decrease in LC3-II expression has been reported in patients with unstable plaques compared to those with stable plaques [48]; such decreases would enable dead cell accumulation in the artery wall and subsequent plaque destabilization ( Figure 2). A dysfunction in the autophagic process, caused by either autophagy related 7 (ATG7) deletion in VSMCs [49,50] or a macrophage-specific ATG5-null mutant mouse model [46], has been linked to atheroma development in AS.…”

PI3K/Akt/mTOR activation by suppression of ELK3 mediates chemosensitivity of MDA-MB-231 cells to doxorubicin by inhibiting autophagy

“…DAPK1 and ATG10, which stimulate autophagy [16,17], were activated, whereas several genes known to activate autophagy, such as DRAM1, ULK2, BCL2L1, EPG5, and NPC1, were suppressed in ELK3 KD [18][19][20][21][22][23][24][25] (Fig. 1A).…”