Effect of simvastatin on atherosclerosis and central aortic pressure in ApoE gene knockout mice / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effects of simvastatin on atherosclerosis and central aortic pressure in ApoE-knockout (ApoE-/-) mice.</p><p><b>METHODS</b>Ten 5-week-old male ApoE-/- mice and 5 C57 mice were fed with high-lipid diet for 3 weeks, and then C57 mice (WT group) and 5 ApoE-/- mice (ApoE-/- group) were given 1% carboxymethyl cellulose solution (8 ml·kg-1·d-1), and another 5 ApoE-/- mice (ApoE-/-/S group) were given simvastatin solution (50 mg·kg-1·d-1) by gavege for 3 weeks. The areas of atherosclerotic lesion in aortic root, central aortic pressure and serum lipid levels were examined.</p><p><b>RESULTS</b>No atherosclerotic plaques were observed in WT group. Compared with ApoE-/- group, simvastatin significantly decreased atherosclerotic lesion area in aortic root (89 818.05±16 980.93 μm2 vs 34 937.01±13 280.65 μm2, P<0.05). The systolic pressure (SP), mean arterial pressure (MAP), pulse pressure (PP) and diastolic pressure (DP) of central aortic pressure were significantly increased in ApoE-/- group compared with those in WT group (P<0.05). Compared to ApoE-/- group, the SP, MAP and PP of central aortic pressure were significantly reduced in ApoE-/-/S group (P<0.05). SP and MAP of central aortic pressure were positively correlated with atherosclerotic lesion area (SP: r=0.7152, P=0.0461; PP: r=0.7594， P=0.0288). Compared with WT group, serum triglyceride, total cholesterol and low-density lipoprotein levels were markedly increased in ApoE-/- group (P<0.05). Serum high-density lipoprotein level was decreased in ApoE-/- group compared with WT group. No differences in serum triglyceride, total cholesterol, low-density lipoprotein and high-density lipoprotein levels were found between ApoE-/- group and ApoE-/-/S group.</p><p><b>CONCLUSION</b>Simvastatin can attenuate atherosclerosis of aorta in ApoE-/- mice, which is associated with the reduced central aortic systolic pressure but not with the serum lipids levels.</p>

Lovastatin protects mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis through activation of PI3K/Akt and ERK1/2 signaling pathways / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigated the effect of lovastatin on hypoxia and serum deprivation (Hypoxia/SD) induced rat MSCs apoptosis in vitro and associated signaling pathway changes.</p><p><b>METHODS</b>MSCs were isolated from Sprague-Dawley rats. The anti-apoptotic effects of lovastatin were detected using Hoechst33342 and annexin V-FITC/PI binding assay by Flow cytometric analysis. The phosphorylation of Akt and ERK1/2, the cytochrome C and the cleaved caspase-3 were detected by Western blot.</p><p><b>RESULTS</b>Lovastatin (0.01 - 1 micromol/L) significantly reduced Hypoxia/SD-induced MSCs apoptosis and increased Akt phosphorylation, reduced caspase-3 activation and cytochrome c release from mitochondria to cytosol in a time dependent manner. These effects could be significantly blocked by both PI3K inhibitor, LY294002 and ERK1/2 inhibitor, U0126.</p><p><b>CONCLUSIONS</b>Our results showed that lovastatin protects MSCs from Hypoxia/SD-induced apoptosis via activating PI3K/Akt and ERK1/2 signaling pathways suggesting a potential role of statins as an adjunct therapeutic agent during transplanting MSCs into damaged heart after myocardial infarction.</p>