RGD Reference Report - Beclin 1 knockdown retards re-endothelialization and exacerbates neointimal formation via a crosstalk between autophagy and apoptosis. - Rat Genome Database

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Beclin 1 knockdown retards re-endothelialization and exacerbates neointimal formation via a crosstalk between autophagy and apoptosis.

Authors: Ye, LX  Yu, J  Liang, YX  Zeng, JS  Huang, RX  Liao, SJ 
Citation: Ye LX, etal., Atherosclerosis. 2014 Nov;237(1):146-54. doi: 10.1016/j.atherosclerosis.2014.08.052. Epub 2014 Sep 6.
RGD ID: 11558011
Pubmed: PMID:25238224   (View Abstract at PubMed)
DOI: DOI:10.1016/j.atherosclerosis.2014.08.052   (Journal Full-text)

OBJECTIVE: Endothelial regeneration is an essential process for the prevention of excessive neointimal formation following endothelial denudation. Beclin 1, a mammalian autophagy gene, is a link between autophagy and apoptosis. We hypothesized that the interference of Beclin 1 can influence re-endothelialization and ultimately affect neointimal formation by regulating autophagy and apoptosis. METHODS: A rat carotid injury model of endothelial denudation was used, and small interfering RNA of Beclin 1 was perivascularly administered. Neointima was evaluated by morphological analysis. von Willebrand factor, Beclin 1, LC3, autophagic substrate p62 and caspase-3 levels were detected by immunofluorescence or Western blotting. Terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling assay was performed to evaluate apoptosis. RESULTS: Carotid injury induced an upregulation of Beclin 1 protein which was down regulated by more than 50% with small RNA interference. Beclin 1 knockdown significantly retarded re-endothelialization 7 days after injury and subsequently augmented neointima by more than 2 folds at 14 and 21 days. Autophagy and apoptosis were detected to reveal the regulatory effect of Beclin 1. The injury-activated autophagy, shown by the increased levels of punctate LC3 and LC3II as well as decreased p62 expression, was significantly inhibited by Beclin 1 knockdown. Meanwhile, the apoptotic endothelial cell number was increased and caspase-3 was up-regulated, though the expression of truncated BID was not significantly influenced. CONCLUSION: Beclin 1 knockdown exacerbated neointimal formation after rat carotid injury, associated with retarded re-endothelialization due to enhanced apoptosis, while simultaneously prohibiting autophagic activation. The data suggested an essential role of Beclin 1 as a regulator between autophagy and apoptosis in the setting of neointimal formation.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BECN1HumanNeointima  ISOBecn1 (Rattus norvegicus) RGD 
Becn1RatNeointima  IMP  RGD 
Becn1MouseNeointima  ISOBecn1 (Rattus norvegicus) RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Becn1Ratautophagy  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Becn1  (beclin 1)

Genes (Mus musculus)
Becn1  (beclin 1, autophagy related)

Genes (Homo sapiens)
BECN1  (beclin 1)


Additional Information