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Vascular smooth muscle cell proliferation depends on caveolin-1-regulated polyamine uptake

In English

Författare

Summary, in English

Much evidence highlights the importance of polyamines for VSMC (vascular smooth muscle cell) proliferation and migration. Cav-1 (caveolin-1) was recently reported to regulate polyamine uptake in intestinal epithelial cells. The aim of the present study was to assess the importance of Cav-1 for VSMC polyamine uptake and its impact on cell proliferation and migration. Cav-1 KO (knockout) mouse aortic cells showed increased polyamine uptake and elevated proliferation and migration compared with WT (wild-type) cells. Both Cav-1 KO and WT cells expressed the smooth muscle differentiation markers SM22 and calponin. Cell-cycle phase distribution analysis revealed a higher proportion of Cav-1 KO than WT cells in the S phase. Cav-1 KO cells were hyper-proliferative in the presence but not in the absence of extracellular polyamines, and, moreover, supplementation with exogenous polyamines promoted proliferation in Cav-1 KO but not in WT cells. Expression of the solute carrier transporters Slc7a1 and Slc43a1 was higher in Cav-1 KO than in WT cells. ODC (ornithine decarboxylase) protein and mRNA expression as well as ODC activity were similar in Cav-1 KO and WT cells showing unaltered synthesis of polyamines in Cav-1 KO cells. Cav-1 was reduced in migrating cells in vitro and in carotid lesions in vivo. Our data show that Cav-1 negatively regulates VSMC polyamine uptake and that the proliferative advantage of Cav-1 KO cells is critically dependent on polyamine uptake. We provide proof-of-principle for targeting Cav-1-regulated polyamine uptake as a strategy to fight unwanted VSMC proliferation as observed in restenosis.

Publiceringsår

2014

Språk

Engelska

Sidor

729-741

Publikation/Tidskrift/Serie

Bioscience Reports

Volym

34

Dokumenttyp

Artikel i tidskrift

Förlag

Portland Press

Ämne

  • Cardiac and Cardiovascular Systems
  • Cell and Molecular Biology

Nyckelord

  • caveolin-1
  • cell cycle
  • ornithine decarboxylase
  • polyamine transporter
  • polyamine
  • vascular smooth muscle cell

Status

Published

Forskningsgrupp

  • Vascular Physiology
  • Cellular Biomechanics
  • Biogenic Amines

ISBN/ISSN/Övrigt

  • ISSN: 0144-8463