Pharmacological induction of HSP27 attenuates intimal hyperplasia in vivo.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Connolly
E M
EM
Departments of Surgery and Pathology, Education and Research Center, Royal College of Surgeons in Ireland, Beaumont Hospital, Beaumont Rd, Dublin 9, Ireland.
Kelly
C J
CJ
Chen
Gang
G
O'grady
T
T
Kay
E
E
Leahy
A
A
Bouchier-Hayes
D J
DJ
D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D016227:Benzoquinones; D015153:Blotting, Western; D002339:Carotid Arteries / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D020212:Carotid Artery Injuries / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000096:biosynthesis; D006360:Heat-Shock Proteins / Q000032:analysis / Q000096:biosynthesis*; D006965:Hyperplasia; D007150:Immunohistochemistry; D019194:Ischemic Preconditioning; D047029:Lactams, Macrocyclic; D008297:Male; D023421:Models, Animal; D018809:Proliferating Cell Nuclear Antigen; D011809:Quinones / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D017828:Rifabutin / Q000031:analogs & derivatives; D017539:Tunica Intima / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D018809:Proliferating Cell Nuclear Antigen; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin