Simvastatin increases circulating endothelial progenitor cells and inhibits the formation of intracranial aneurysms in rats with diet-induced hyperhomocysteinemia.
BACKGROUND AND PURPOSE
Endothelial dysfunction triggers early pathological changes in artery, leading to the formation of intracranial aneurysm (ICA). Increase in plasma homocysteine (Hcy) impairs endothelium and endothelial progenitor cells (EPCs) are critical in repairing damaged endothelium. The aim of this study was to assess the impact of simvastatin on ICA formation in rats with hyperhomocysteinemia (HHcy).


METHODS
ICAs were induced in Male Sprague-Dawley rats after surgical induction in the presence of HHcy induced by a high L-methionine diet with or without oral simvastatin treatment. The size and media thickness of ICAs were evaluated 2 months after aneurysm induction. EPCs and serum vascular endothelial grow factor (VEGF) were measured be flow cytometry and ELISA respectively. Plasma Hcy levels and expression of VEGF, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), matrix metalloproteinase-2 (MMP-2), and MMP-9 in aneurysmal walls were examined and correlated with ICA formation.


RESULTS
HHcy accelerates ICA formation and rats treated with simvastatin exhibited a significant increase in media thickness and a reduction in aneurysmal size. Simvastatin increased levels of circulating EPCs and decreased iNOS, MMP-2, MMP-9 and VEGF mRNA levels, while increased eNOS mRNA in aneurysmal tissue.


CONCLUSION
In a rat model, HHcy reduces circulating EPCs and accelerates ICA formation. Simvastatin treatment increases circulating EPCs and inhabits the formation of ICA. We have shown a close association among circulating EPCs, biochemical markers related to vascular remodeling and the formation of ICA.
['Xu|Yong|Y|', 'Zhang|Bin|B|', 'Chen|Yu|Y|', 'Wang|Xiu|X|', 'Li|Yong|Y|', 'Wu|Jiangping|J|', 'Dong|Hao|H|', 'Wang|Shuo|S|']
Simvastatin Endothelial progenitor cells Hyperhomocysteinemia Homocysteine Intracranial cerebral aneurysm