Rosuvastatin for enhancement of aneurysm neck endothelialization after coil embolization: promotion of endothelial progenitor cells in a rodent model

Abstract

OBJECT Coil embolization is a safe, efficient, and minimally invasive technique for the treatment of intracranial aneurysms. However, coil embolization is associated with a higher risk of recurrence than clip ligation. In this study, the authors explore a new approach through the promotion of endothelial progenitor cells (EPCs) to optimize endothelialization of the aneurysm neck and reduce the risk of recurrence. METHODS A coiled aneurysm model was created in 48 adult male Sprague-Dawley rats via microsurgery. Half of these animals were treated with rosuvastatin (20 mg/kg) in saline via gavage for 10, 20, or 30 days. The other half were administered saline without rosuvastatin. An additional 15 rats underwent "mock surgery" (identical anesthesia and saline gavage but no surgery). The endothelial repair process in the coiled aneurysms was evaluated via flow cytometry, im-munostaining, and electronic microscopy. The mock surgery group was used for comparison in flow cytometry studies. The effects of rosuvastatin on viability and functioning of Sprague-Dawley rat bone marrow-derived EPCs were also explored via MTT, migration, and tube formation assays. RESULTS The aneurysm neck repair score was significantly higher in the rosuvastatin-treated rats than in the untreated rats (p < 0.05). The circulating EPC count was increased and maintained at a higher level in rosuvastatin-treated rats compared with the aneurysm rats that did not receive rosuvastatin (p < 0.05). Immunostaining showed that the aneurysm neck endothelium was more integrated and the number of kinase insert domain receptor-positive cells was increased in the rosuvastatin-treated rats. Further study demonstrated that rosuvastatin promoted EPC proliferation, migration, and tube formation. CONCLUSIONS Rosuvastatin promoted endothelialization of the coiled aneurysm neck via induction of EPCs, suggesting that promoting endothelialization provides an additional therapeutic opportunity during vascular endothelium repair.

Keywords: DMSO = dimethylsulfoxide; EPC = endothelial progenitor cell; GDC = Guglielmi detachable coil; H & E = hematoxylin and eosin; KDR = kinase inert domain receptor; MTT = 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide; OD = optical density; SEM = scanning electron microscope; aneurysm; endothelial progenitor cells; endothelialization; rosuvastatin; vWF = von Willebrand factor; vascular disorders.