Pharmacological induction of HSP27 attenuates intimal hyperplasia in vivo.

Abstract

OBJECTIVES:

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.

MATERIALS AND METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: E M Connolly, C J Kelly, Gang Chen, T O'grady, E Kay, A Leahy, D J Bouchier-Hayes
• Journal: European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery (Eur J Vasc Endovasc Surg) Vol. 25 Issue 1 Pg. 40-7 (Jan 2003) ISSN: 1078-5884 [Print] England
• PMID: 12525810 (Publication Type: Evaluation Study, Journal Article)

Chemical References

• Benzoquinones
• Enzyme Inhibitors
• HSP70 Heat-Shock Proteins
• Heat-Shock Proteins
• Lactams, Macrocyclic
• Proliferating Cell Nuclear Antigen
• Quinones
• Rifabutin
• herbimycin

Topics

• Angioplasty, Balloon (adverse effects)
• Animals
• Benzoquinones
• Blotting, Western
• Carotid Arteries (chemistry, drug effects, pathology)
• Carotid Artery Injuries (etiology, metabolism, pathology, prevention & control)
• Enzyme Inhibitors (pharmacology)
• HSP70 Heat-Shock Proteins (analysis, biosynthesis)
• Heat-Shock Proteins (analysis, biosynthesis)
• Hyperplasia
• Immunohistochemistry
• Ischemic Preconditioning
• Lactams, Macrocyclic
• Male
• Models, Animal
• Proliferating Cell Nuclear Antigen
• Quinones (pharmacology)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Recurrence
• Rifabutin (analogs & derivatives)
• Tunica Intima (chemistry, drug effects, pathology)