Zoledronate inhibits intimal hyperplasia in balloon-injured rat carotid artery.
OBJECTIVE
Zoledronate has been reported to inhibit the proliferation, adhesion and migration of vascular smooth muscle cells. In the present study, we assessed whether systemic and local delivery of zoledronate would be sufficient to prevent intimal hyperplasia.


METHODS
Twenty-four male Sprague-Dawley rats were assigned into four groups: non-treated group, systemic zoledronate-treated group, local collagen-treated group and local zoledronate-treated group. All four groups underwent balloon injury to the right common carotid artery. The left uninjured carotid arteries of the non-treated group were considered as normal artery samples. Twenty-one days after arterial injury and treatment, the right and left common carotid arteries were fixed, sectioned, stained and measured by computer-aided image analysis.


RESULTS
At 3 weeks, there was a 59% reduction of the intima/media area ratio in the systemic zoledronate-treated group compared with the non-treated group (P < 0.01). There was an 87% reduction of the intima/media area ratio in the local zoledronate-treated group compared with the local collagen-treated group (P < 0.01).


CONCLUSIONS
Both systemic and local delivery of zoledronate correspond to a significant reduction in intimal hyperplasia seen at 3 weeks.
Department of General Surgery, Huashan Hospital of Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China.
L
L
Wu
L
L
Zhu
W H
WH
Shi
B
B
Yu
D
D
Cai
D000287:Administration, Topical; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004164:Diphosphonates / Q000008:administration & dosage*; D004195:Disease Models, Animal; D006965:Hyperplasia; D007091:Image Processing, Computer-Assisted; D007093:Imidazoles / Q000008:administration & dosage*; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D000077211:Zoledronic Acid
D002317:Cardiovascular Agents; D004164:Diphosphonates; D007093:Imidazoles; D018809:Proliferating Cell Nuclear Antigen; D000077211:Zoledronic Acid