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Autophagic marker MAP1LC3B expression levels are associated with carotid atherosclerosis symptomatology.

Swaminathan B, Goikuria H, Vega R, Rodríguez-Antigüedad A, López Medina A, Freijo Mdel M, Vandenbroeck K, Alloza I - PLoS ONE (2014)

Bottom Line: Several 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.

View Article: PubMed Central - PubMed

Affiliation: Neurogenomiks, Neurosciences Department, Faculty of Medicine and Odontology, University of Basque Country, Leioa, Spain.

ABSTRACT

Objectives: The 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).

Methods: 80 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.

Results: Several 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.

Conclusions: Carotid 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.

No MeSH data available.


Related in: MedlinePlus

Correlation networks.The correlation has been computed as the normalised conditional mutual information. Only correlations above 0.7 are shown in this figure and with a significance of P<0.001.
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pone-0115176-g002: Correlation networks.The correlation has been computed as the normalised conditional mutual information. Only correlations above 0.7 are shown in this figure and with a significance of P<0.001.

Mentions: Correlation analysis between each of the 59 of genes tested in this study was performed using Spearman's rank correlation test using the GraphPad Prism software version 5.0. VCAM1 was correlated with TGFB1 (r = 0.9), MANF (r = 0.86), THBS1 (r = 0.83) and TNF (r = 0.7). On the other hand, ELANE was found to be correlated with IL10 and ELN (r value of 0.9 and 0.71 respectively) while ELN was as well correlated with TGFB1 (r = 0.7). Thus, the correlation analysis identified a pattern of genes that cluster together significantly. Fig. 2 shows correlation values between genes with significant (P<0.001) r value higher than 0.7.


Autophagic marker MAP1LC3B expression levels are associated with carotid atherosclerosis symptomatology.

Swaminathan B, Goikuria H, Vega R, Rodríguez-Antigüedad A, López Medina A, Freijo Mdel M, Vandenbroeck K, Alloza I - PLoS ONE (2014)

Correlation networks.The correlation has been computed as the normalised conditional mutual information. Only correlations above 0.7 are shown in this figure and with a significance of P<0.001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4264866&req=5

pone-0115176-g002: Correlation networks.The correlation has been computed as the normalised conditional mutual information. Only correlations above 0.7 are shown in this figure and with a significance of P<0.001.
Mentions: Correlation analysis between each of the 59 of genes tested in this study was performed using Spearman's rank correlation test using the GraphPad Prism software version 5.0. VCAM1 was correlated with TGFB1 (r = 0.9), MANF (r = 0.86), THBS1 (r = 0.83) and TNF (r = 0.7). On the other hand, ELANE was found to be correlated with IL10 and ELN (r value of 0.9 and 0.71 respectively) while ELN was as well correlated with TGFB1 (r = 0.7). Thus, the correlation analysis identified a pattern of genes that cluster together significantly. Fig. 2 shows correlation values between genes with significant (P<0.001) r value higher than 0.7.

Bottom Line: Several 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.

View Article: PubMed Central - PubMed

Affiliation: Neurogenomiks, Neurosciences Department, Faculty of Medicine and Odontology, University of Basque Country, Leioa, Spain.

ABSTRACT

Objectives: The 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).

Methods: 80 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.

Results: Several 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.

Conclusions: Carotid 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.

No MeSH data available.


Related in: MedlinePlus