Effects of simvastatin on vasa vasorum and aortic endothelial function in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of hyperlipidemia on vasa vasorum and vascular endothelial growth factor (VEGF) and study the role of vasa vasorum in arteriosclerosis.</p><p><b>METHODS</b>Thirty SD rats were randomized into normal control, hyperlipidemic and simvastatin treatment groups (n=10). In simvastatin group, hyperlipidemia was induced by a 4-week administration of atherogenic diet followed by a 16-week treatment with simvastatin at the daily dose of 10 mg/kg, and the rats in hyperlipidemic rats received no treatment. The changes in the aorta and vasa vasorum were examined, and serum lipid concentration and VEGF and NO levels were measured.</p><p><b>RESULTS</b>Compared with the control group, the hyperlipidemic rats showed significantly thickened intima and media aorta and increased vasa vasorum density with lowered NO level, but VEGF underwent no significant changes. Simvastatin treatment significantly reduced the thickness of the intima and media aorta and increased vasa vasorum density in comparison with those in hyperlipidemic group. Simvastatin treatment also significantly increased VEGF and NO levels and a positive correlation was noted between their levels.</p><p><b>CONCLUSION</b>Hyperlipidemia can impair the vasa vasorum and aortic endothelial function. Simvastatin increases VEGF and NO and promotes neogenesis of the vasa vasorum for the benefit of the aortic function.</p>

Leptin promotes neointimal formation by stimulating vascular smooth muscle cell proliferation through leptin receptor / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the role of leptin in neointimal formation and related mechanisms.</p><p><b>METHODS</b>Femoral arterial injury was induced in wild-type (Wt, n = 10), leptin-deficient (Lep(-)/-, n = 12), and leptin receptor-deficient (LepR(-)/-, n = 10) mice. Leptin treatment studies (tail vein injection of adenovirus expressing murine leptin on the RSV promoter, ad-leptin) were performed on Lep(-)/- (n = 5) and LepR(-)/- (n = 4) mice. Intimal (I) and medial (M) areas were measured and the ratio of I/M was calculated. Smooth muscle cells were detected by smooth muscle alpha-actin staining using an alpha-actin monoclonal antibody. Cellular proliferation was analyzed with BrdU Staining Kit and the number of BrdU-positive cells was counted manually. Plasma leptin level was measured by ELISA.</p><p><b>RESULTS</b>The I/M ratio of Lep(-)/- and LepR(-)/- mice was significantly lower than that in Wt separately (Lep(-)/- vs. Wt = 0.80 +/- 0.14 vs. 1.50 +/- 0.22, P < 0.01; LepR(-)/- vs. Wt = 0.55 +/- 0.20 vs. 1.50 +/- 0.22, P < 0.05). Plasma leptin level was significantly increased in Lep(-)/- and LepR(-)/- mice post leptin treatment. I/M was significantly increased in Lep(-)/- mice receiving ad-leptin compared with untreated Lep(-)/- mice (P < 0.05), while I/M was similar between LepR(-)/- mice with and without ad-leptin treatment (P > 0.05). The changes on number of positive alpha-actin and BrdU stained smooth muscle cells were consistent with the neointimal formation findings in various groups.</p><p><b>CONCLUSIONS</b>Mice lacking leptin or the leptin receptor were protected from neointimal formation following vascular injury. Leptin treatment increased neointimal formation in Lep(-)/- but not in LepR(-)/- mice, suggesting leptin receptor activation and vascular smooth muscle cell proliferation played a pivotal role on neointimal formation post-injury in this model, giving an evidence that high plasma leptin level is a risk factor for neointimal formation.</p>

Factor V Leiden mutation leads to enhanced atherosclerosis in apolipoprotein E deficient mice / 中华心血管病杂志

<p><b>OBJECTIVE</b>Factor V Leiden (FvL) causing activated protein C resistance is a genetic risk factor for venous thrombosis in humans, and it's effect on atherosclerosis is controversial. We evaluated the effect of FvL mutation on atherosclerosis in apolipoprotein E deficient mice fed with normal diet.</p><p><b>METHODS</b>Degree of atherosclerosis and tissue fibrin deposition were determined in Fv+/+ApoE-/-, FvQ/+ApoE-/- and FvQ/QApoE-/- mice.</p><p><b>RESULTS</b>In the presence of ApoE deficiency, homozygous FvL significantly increased atherosclerosis coverage in ApoE-/- mice (FvQ/QApoE-/- vs. Fv+/+ApoE-/-=5.0%+/-1.1% vs. 2.2%+/-0.4%, P<0.005) and tissue fibrin deposition in atherosclerotic lesion (FvQ/QApoE-/- vs. Fv+/+ApoE-/-=3.4% +/- 0.5% vs. 1.8%+/-0.4%, P<0.05). The atherosclerotic lesion of FvQ/+ApoE-/- mice was intermediate between FvQ/Q ApoE-/- and Fv+/+ApoE-/-, and there was no significant difference comparing with any of them.</p><p><b>CONCLUSIONS</b>These observations demonstrate that homozygous FvL could promote atherosclerosis and fibrin deposition in apolipoprotein E deficient mice suggesting that Factor V mutation could be an important genetic risk factor for the enhanced atherosclerosis in human.</p>

Triptolide-eluting stent prevents porcine coronary artery in-stent restenosis by affecting PCNA and P27(kip1) expression / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effectiveness and safety of triptolide-eluting stents implanted in porcine coronary arteries for restenosis prevention, and its effect on the expression of proliferating cell nuclear antigen (PCNA) and P27(kip1).</p><p><b>METHODS</b>Ten triptolide-eluting stents and 10 stainless steel stents (control) were implanted in 20 porcine coronary arteries at random. Four weeks later, angiography of the arteries was performed along with also histopathological and immunochemical examinations.</p><p><b>RESULTS</b>The in-stent minimal lumen diameter of triptolide group was significantly greater, and the neointimal area significantly smaller, than those of the control group (P<0.05). PCNA expression was significantly lower while P27(kip1) protein significantly higher in triptolide group than in the control group (P<0.05).</p><p><b>CONCLUSION</b>Triptolide-eluting stent can effectively inhibit neointimal formation to prevent restenosis in porcine coronary artery 4 weeks after implantation, probably by inhibiting P27(kip1) expression and consequently vascular smooth muscle cell proliferation.</p>

Isolation, in vitro culture and identification of cardiac stem cells from neonatal SD rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To isolate and culture cardiac stem cells (CSCs) in vitro and evaluate their potential of differentiation into functional cardiac myocytes.</p><p><b>METHODS</b>Myocardial tissues obtained from neonatal SD rats were cut into pieces of 0.5-1.0 mm(3), and digested twice for 5 min at 37 degrees C; with 0.2% trypsin and 0.1% collagenase II. The remaining tissues were cultured in complete explant culture medium (CEM) at 37 degrees C; in the presence of 5% CO(2). About a week later, a layer of fibroblast-like cells was generated from the adherent explants. These cells were passaged and seeded at about 1x10(6) cells/ml in poly-D-lysine-coated multi-well plates in cardiosphere-growing medium. When beating of the cultured cells was observed (at week 2), flow cytometry and immunohistochemistry were performed for identification of the primary and passaged cells.</p><p><b>RESULTS</b>The primary cells were successfully cultured from the digested myocardial tissue, and flow cytometry demonstrated the phenotype of c-kit(+)CD31(+)CD34(-)CD45(-)CTnT(-). After cell passage for about two weeks, single beating cells and cell clusters with synchronized contraction were seen microscopically, and their phenotype was converted to c-kit(+)CD31(-)CD34(-)CD45(-) CTnT(+). Immunohistochemistry staining identified CTnT expression in the passaged cells but not in the primary cells.</p><p><b>CONCLUSIONS</b>A cell population with the phenotype c-kit(+)CD31(+)CD34(-)CD45(-)CTnT(-) has been obtained from neonatal SD rat heart, which possesses the potential to differentiate in vitro into beating cardiac myocytes and express CTnT protein.</p>