In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 36, No. suppl_1 ( 2016-05)
Abstract:
Introduction: Oral statin administration reduces intimal hyperplasia (IH) after arterial injury by only ~25%. Alternative drug delivery systems have gained attention as carriers for hydrophobic drugs. We studied the effects of simvastatin (free vs hyaluronic acid tagged polysialic acid-polycaprolactone micelles) in vitro on vascular smooth muscle cell (VSMC) migration and in vivo after arterial injury. We hypothesized both free and micelles containing statins would inhibit VSMC chemotaxis and local statin treatment would reduce IH in Sprague-Dawley (SD) rats following carotid balloon injury greater than oral delivery. Methods: VSMCs pretreated with free simvastatin (1 μM, 20 min or 20 hrs) or simvastatin-loaded micelles underwent chemotaxis to thrombospondin-1 (20 μg/mL) or serum-free media using a modified Boyden chamber. Next, SD rats (13-15 wks) who underwent balloon injury of the common carotid artery (5 atm/5 min) received statin therapy – either intraluminal simvastatin loaded micelles (50 μM, pressurized for 5 min) prior to injury or periadventitial pluronic gel (50 μM simvastatin) following injury. Arteries were harvested 14 days postoperatively. Morphometric analysis was performed using the intimal/media area ratio defined as intima/(intima + media). Findings were compared to our historic animals which received oral simvastatin (10 mg/kg/day) or controls without statin therapy. Statistical analysis was by ANOVA and p 〈 0.05 was significant. Results: Simvastatin loaded micelles and free simvastatin inhibited VSMC chemotaxis (54%-60%, p 〈 0.05). IH was induced in all injured vessels. Simvastatin in pluronic gel or micelles reduced IH compared to untreated controls (0.208 ± 0.04 or 0.160 ± 0.03 vs 0.350 ± 0.03, respectively, p 〈 0.05). However, neither gel nor simvastatin-loaded micelles were superior to oral statins (0.261 ± 0.03, p 〉 0.05). Conclusions: Intraluminally and periadventially delivered statins were effective in reducing IH. The efficacy of single dose, locally delivered statins alone may lead to novel treatment modalities for the prevention of IH. The different routes of administration allow for treatment at the time of both open and endovascular procedures, without the need for systemic therapy.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.36.suppl_1.174
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2016
detail.hit.zdb_id:
1494427-3
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