Effect of alpha-galactosidase A deficiency on FV leiden fibrin deposition and thrombosis in mice / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of alpha-galactosidase A (Gla) deficiency on FV Leiden (FVL) associated thrombosis in vivo.</p><p><b>METHODS</b>To generate the mice carrying mutations in Gla and FVL and analyze the tissue fibrin deposition in organs and thrombosis.</p><p><b>RESULTS</b>In the presence of FVL, Gla deficiency greatly increased tissue fibrin deposition compared with that in wild-type [Gla(-/0) FV(Q/Q) vs. Gla(+/0) FV(Q/Q) = (0.24 +/- 0.07)% vs. (0.086 +/- 0.049)%, P < 0.0001; Gla(-/-) FV(Q/Q) vs. Gla(+/+) FV(Q/Q) = (0.32 +/- 0.03)% vs. (0.06 +/- 0.005)%, P < 0.05]. With Gla deficiency, the number of thrombi on organ sections in FVL mice was significantly increased [(Gla(-/-) FV(Q/Q) and Gla(-/0) FV(Q/Q)) vs. (Gla(+/+) FV(Q/Q) and Gla(+/0) FV(Q/Q)) = 1.9 +/- 0.7 vs. 0.3 +/- 0.1, P < 0.05].</p><p><b>CONCLUSIONS</b>Gla deficiency could be an important genetic modifier for the enhanced thrombosis associated with FVL.</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>

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>