Inhibition of PDGF-BB-induced proliferation and migration in VSMCs by proanthocyanidin A2: Involvement of KDR and Jak-2/STAT-3/cPLA2 signaling pathways

Biomed Pharmacother. 2018 Feb:98:847-855. doi: 10.1016/j.biopha.2018.01.010. Epub 2018 Jan 6.

Abstract

Proanthocyanidin A2 (PA2), one of A-type proanthocyanidins, has been shown to harbor a broad spectrum of pharmacological activities, including anti-inflammatory, antioxidant, anti-HIV, anti-CDV and anti-?-glucosidase activities. However, little is known about the role for PA2 in regulating PDGF-induced VSMC proliferation and migration. In the present study, we investigated the possible effects of PA2 on PDGF-BB-induced proliferation, migration and inflammation in VSMCs in vitro to mimic a postangioplasty PDGF shedding condition. Herein, the data clearly show that PA2 markedly inhibited proliferation, migration and inflammatory responses at 0-30??g/ml concentration in VSMCs in vitro. 10-30??g/ml PA2 inhibited PDGF-mediated NAD(P)H oxidase activation and intracellular ROS formation in VSMCs. Furthermore, the effects exerted by PA2 involve the participation of KDR and Jak-2/STAT-3/cPLA2 signaling pathways. These data also highlight the possible therapeutic use of PA2 in vascular proliferative diseases, where abnormal proliferation and migration play important pathological roles.

Keywords: Jak2; KDR; Migration; PDGF; Procyanidin A2; Proliferation.

MeSH terms

  • Animals
  • Becaplermin
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Female
  • Janus Kinase 2 / metabolism*
  • Muscle, Smooth, Vascular / cytology*
  • Myocytes, Smooth Muscle / cytology*
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • Phospholipases A2, Cytosolic / metabolism*
  • Proanthocyanidins / chemistry
  • Proanthocyanidins / pharmacology
  • Proto-Oncogene Proteins c-sis / pharmacology*
  • Rats, Sprague-Dawley
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*

Substances

  • Proanthocyanidins
  • Proto-Oncogene Proteins c-sis
  • STAT3 Transcription Factor
  • Becaplermin
  • proanthocyanidin A2
  • Kdr protein, rat
  • Vascular Endothelial Growth Factor Receptor-2
  • Janus Kinase 2
  • Phospholipases A2, Cytosolic