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(Stroke. 2008;39:1022.)
© 2008 American Heart Association, Inc.

Research Letters

Reverse Regulation of Endothelial Cells and Myointimal Hyperplasia on Cell Proliferation by a Heatshock Protein-Coinducer After Hypoxia

Laszlo Denes, PhD; Zoltan Bori, MS; Eva Csonka, DSc; Laszlo Entz, MD, PhD Zoltan Nagy, MD, DSc

From the National Stroke Centre (L.D., Z.B., E.C., Z.N.), National Institute of Psychiatry and Neurology, Section of Vascular Neurology; Department of Vascular Surgery (L.E.), Semmelweis University, Budapest, Hungary.

Correspondence to Laszlo Denes, PhD, National Stroke Centre, National Institute of Psychiatry and Neurology, H 1021 Budapest, Hüvösvölgyi str. 116, Hungary. E-mail dr.denes{at}gmail.com

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.

Key Words: carotid stenosis • endothelium • heatshock-protein • proliferation • smooth muscle cells