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  • Pharmacological induction of HSP27 attenuates intimal hyperplasia in vivo.

Pharmacological induction of HSP27 attenuates intimal hyperplasia in vivo.

European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery (2003-01-15)
E M Connolly, C J Kelly, Gang Chen, T O'grady, E Kay, A Leahy, D J Bouchier-Hayes
ABSTRACT

intimal hyperplasia (IH) is a major cause of re-stenosis post-vascular intervention. Induction of heat shock proteins (HSPs), by thermal pre-conditioning, reduces IH. Our aim was to investigate the effect of the pharmacological HSP inducer herbimycin A on IH in the rat carotid balloon injury model. thirty male Sprague-Dawley rats were randomized into three groups. All groups underwent balloon injury to the left carotid artery. Stress proteins were induced 18 h pre-operatively by heat shock or herbimycin A. Two weeks post-operatively, animals were sacrificed and carotid intima/media area ratio (I/M ratio) calculated using computerized planimetry. Neo-intimal proliferation was assessed immunohistochemically with PCNA (proliferating cell nuclear antigen). Western blot and immunohistochemistry for arterial HSP70 and HSP27 were performed. heat stress and herbimycin significantly reduced the I/M ratio (p < 0.05 vs balloon injury alone). Neo-intimal proliferation was significantly reduced in the heat stress and herbimycin groups (p < 0.05 vs balloon injury alone). Heat stress induced arterial HSP70 and HSP27. Herbimycin A increased arterial HSP27. herbimycin A significantly attenuates IH after balloon injury. HSP27 may be the HSP involved in mediating this response. Pharmacological inducers of HSPs may have a therapeutic role to play in preventing re-stenosis post-vascular intervention.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Herbimycin A from Streptomyces hygroscopicus, ≥95% (HPLC), powder