ß3-integrin inhibits lipopolysaccharide-induced autophagy in cardiomyocytes via the Akt signaling pathway

Cardiology. 2015;130(4):249-59. doi: 10.1159/000371489.


Objective: To investigate the role of β 3 -integrin in lipopolysaccharide (LPS)-induced autophagy in cardiomyocytes and its underlying mechanism.

Methods: β 3 -Integrin expression in cardiomyocytes was up- or downregulated by adenovirus transfection or cyclic arginine-glycine-aspartic acid (cRGD) peptide treatment before LPS stimulation. The expression of autophagy-associated proteins (LC3-II, Beclin-1 and Bcl-2) and the activation of Akt were determined using Western blotting. Autophagosomes and autophagic vacuoles were observed using monodansylcadaverine (MDC) dye and transmission electron microscopy, respectively.

Results: Downregulation of β 3 -integrin with cRGD peptide resulted in enhanced LC3-II and Beclin-1 and decreased Bcl-2 expression. Low Beclin-1 levels were detected after LPS stimulation in adenovirus β 3 -integrin-transfected cardiomyocytes. There was no significant difference in LC3-II levels between control and adenovirus β 3 -integrin-transfected cardiomyocytes. Enhanced accumulation of MDC dye and autophagosomes, which were inhibited by β 3 -integrin overexpression, were detected after LPS treatment. The increased phosphorylation of Akt after LPS stimulation was inhibited by cRGD and enhanced by β 3 -integrin overexpression. Furthermore, the Akt inhibitor triciribine inhibited the negative effect of β 3 - integrin on autophagy, as shown by LC3-II and Beclin-1 upregulation.

Conclusions: β 3 -Integrin inhibits LPS-induced autophagy in cardiomyocytes. The inhibition of Akt signaling might be an important mechanism in this process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy*
  • Beclin-1
  • Humans
  • Integrin beta3 / genetics*
  • Lipopolysaccharides / adverse effects
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Microscopy, Electron
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / ultrastructure
  • Peptides, Cyclic / therapeutic use
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction*
  • Transfection


  • Apoptosis Regulatory Proteins
  • BCL2 protein, human
  • BECN1 protein, human
  • Beclin-1
  • Integrin beta3
  • Lipopolysaccharides
  • MAP1LC3A protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Peptides, Cyclic
  • Proto-Oncogene Proteins c-bcl-2
  • cyclic arginine-glycine-aspartic acid peptide
  • Proto-Oncogene Proteins c-akt