title: Autophagic marker MAP1LC3B expression levels are associated with carotid atherosclerosis symptomatology.
abstract: OBJECTIVE
  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.
authors.affiliation: Neurogenomiks, Neurosciences Department, Faculty of Medicine and Odontology, University of Basque Country, Leioa, Spain.
authors.forename: Bhairavi
authors.initials: B
authors.lastname: Swaminathan
authors.affiliation: Neurogenomiks, Neurosciences Department, Faculty of Medicine and Odontology, University of Basque Country, Leioa, Spain; Achucarro Basque Center for Neurosciences, Zamudio, Spain.
authors.forename: Haize
authors.initials: H
authors.lastname: Goikuria
authors.affiliation: Department of Neurology, Basurto Hospital, Bilbao, Spain.
authors.forename: Reyes
authors.initials: R
authors.lastname: Vega
authors.affiliation: Department of Neurology, Basurto Hospital, Bilbao, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Rodríguez-Antigüedad
authors.affiliation: Department of Neurology, Basurto Hospital, Bilbao, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: López Medina
authors.affiliation: Department of Neurology, Basurto Hospital, Bilbao, Spain.
authors.forename: María del Mar
authors.initials: Mdel M
authors.lastname: Freijo
authors.affiliation: Neurogenomiks, Neurosciences Department, Faculty of Medicine and Odontology, University of Basque Country, Leioa, Spain; IKERBASQUE, Basque Foundation for Sciences, Bilbao, Spain; Achucarro Basque Center for Neurosciences, Zamudio, Spain.
authors.forename: Koen
authors.initials: K
authors.lastname: Vandenbroeck
authors.affiliation: Neurogenomiks, Neurosciences Department, Faculty of Medicine and Odontology, University of Basque Country, Leioa, Spain; IKERBASQUE, Basque Foundation for Sciences, Bilbao, Spain; Achucarro Basque Center for Neurosciences, Zamudio, Spain.
authors.forename: Iraide
authors.initials: I
authors.lastname: Alloza
mesh_terms: D000368:Aged; D001343:Autophagy / Q000502:physiology; D015415:Biomarkers; D002340:Carotid Artery Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016893:Carotid Stenosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins