Reverse regulation of endothelial cells and myointimal hyperplasia on cell proliferation by a heatshock protein-coinducer after hypoxia.
OBJECTIVE
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.
Denes
Laszlo
L
Bori
Zoltan
Z
Csonka
Eva
E
Entz
Laszlo
L
Nagy
Zoltan
Z
D000368:Aged; D001921:Brain / Q000098:blood supply; D002196:Capillaries / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology*; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D006965:Hyperplasia; D000860:Hypoxia / Q000473:pathology*; D008875:Middle Aged; D010078:Oxazines / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology*
D006360:Heat-Shock Proteins; D010078:Oxazines; D010880:Piperidines; C469852:iroxanadine