Pharmacological induction of HSP27 attenuates intimal hyperplasia in vivo

• Published in: European journal of vascular and endovascular surgery Vol. 25; no. 1; pp. 40 - 47
• Main Authors: Connolly, E.M., Kelly, C.J., Chen, Gang, O'Grady, T., Kay, E., Leahy, A., Bouchier-Hayes, D.J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2003
• Subjects: Angioplasty, Balloon - adverse effects; Animals; Benzoquinones; Blotting, Western; Carotid Arteries - chemistry; Carotid Arteries - drug effects; Carotid Arteries - pathology; Carotid Artery Injuries - etiology; Carotid Artery Injuries - metabolism; Carotid Artery Injuries - pathology; Carotid Artery Injuries - prevention & control; Enzyme Inhibitors - pharmacology; Heat shock proteins; Heat-Shock Proteins - analysis; Heat-Shock Proteins - biosynthesis; Herbimycin A; HSP70 Heat-Shock Proteins - analysis; HSP70 Heat-Shock Proteins - biosynthesis; Hyperplasia; Immunohistochemistry; Intimal hyperplasia; 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; Tunica Intima - drug effects; Tunica Intima - pathology; Heat shock proteins; Herbimycin A; Intimal hyperplasia
• ISSN: 1078-5884; 1532-2165
• DOI: 10.1053/ejvs.2002.1793

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. Eur J Vasc Endovasc Surg 25, 40–47 (2003)