Human cathelicidin LL-37 inhibits platelet aggregation and thrombosis via Src/PI3K/Akt signaling

Biochem Biophys Res Commun. 2016 Apr 22;473(1):283-289. doi: 10.1016/j.bbrc.2016.03.095. Epub 2016 Mar 21.

Abstract

Biological functions of human cathelicidin LL-37 have been widely reported, including antibacterial, immune and anti-tumor effects. However, the antiplatelet activity of LL-37 has not been addressed. The purpose of our study was to investigate the antiplatelet and antithrombotic actions of LL-37. We found that this peptide inhibited human platelet aggregation in vitro and attenuated thrombus formation in vivo. Furthermore, LL-37 reduced phosphorylation of Src kinase and Akt(Ser473), decreased platelet spreading on immobilized fibrinogen and inhibited P-selectin expression on platelets. These results demonstrate that LL-37 has antiplatelet and antithrombotic actions.

Keywords: Antiplatelet; Antithrombosis; LL-37; Src/PI3K/Akt signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / chemistry*
  • Blood Platelets / metabolism
  • Cathelicidins
  • Female
  • Fibrinogen / chemistry
  • Gene Expression Regulation
  • Humans
  • Male
  • P-Selectin / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation
  • Platelet Activation / drug effects
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / chemistry
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Thrombosis / drug therapy*
  • src-Family Kinases / metabolism*

Substances

  • Antimicrobial Cationic Peptides
  • P-Selectin
  • Platelet Aggregation Inhibitors
  • Fibrinogen
  • src-Family Kinases
  • AKT1 protein, human
  • Akt1 protein, rat
  • Proto-Oncogene Proteins c-akt
  • Cathelicidins