Reverse regulation of endothelial cells and myointimal hyperplasia on cell proliferation by a heatshock protein-coinducer after hypoxia

Laszlo Denes, Zoltan Bori, Eva Csonka, Laszlo Entz, Zoltan Nagy

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Abstract

BACKGROUND AND PURPOSE - Myointimal hyperplasia (MIH) cells are related to permanent upregulated proliferation as tumor-like cells. The aim of this study is to assess whether treatment of cells after hypoxia by Iroxanadine heat-shock protein (HSP-coinducer) predicts recovery through cell proliferation. METHODS - Vascular smooth muscle cells (VSMC) and brain capillary endothelial cells (HBEC) were isolated from human origin and MIH-cells from early carotid restenosis after surgery. Cell proliferation was quantified by bromuridine (BrdU) incorporation after hypoxia/reoxygenation. HSP72 and cyclin-dependent kinase (CDKN1A) mRNA expression was assessed by reverse transcription-polymerase chain reaction (PCR) and cell cycle distribution by flow cytometry (FACS) analysis. RESULTS - After hypoxia/reoxygenation, the proliferation of MIH-cells increased, whereas endothelial cells decreased (MIH: 0.266±0.016 versus 0.336±0.024; P<0.05; HBEC: 1.249±0.10 versus 0.878±0.11; P<0.05). Whereas augmented proliferation of MIH-cells was reduced (40% to 45%) by HSP-coinducer, diminished HBEC proliferation increased (46.2%). Stress-activated-protein-kinase (SAPK)p38-dependent cell cycle redistribution was generated by an increase in HSP72 and CDKN1A mRNA levels in MIH-cells. CONCLUSIONS - The 2 key players of early restenosis (MIH, EC) were oppositely regulated and correspondingly after treatment by HSP-coinducer reverse recovered. Drug candidate may have therapeutic potential in (re)restenosis.

Original languageEnglish
Pages (from-to)1022-1024
Number of pages3
JournalStroke
Volume39
Issue number3
DOIs
Publication statusPublished - Mar 1 2008

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Keywords

  • Carotid stenosis
  • Endothelium
  • Heatshock-protein
  • Proliferation
  • Smooth muscle cells

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

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