Plasminogen Deficiency Significantly Reduces Vascular Wall Disease in a Murine Model of Type IIa Hypercholesterolemia.
Plasminogen Deficiency Significantly Reduces Vascular Wall Disease in a Murine Model of Type IIa Hypercholesterolemia.
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在IIa型高胆固醇血症小鼠模型中，纤溶酶原缺乏显著减少血管壁疾病。
DOI：
10.3390/biomedicines9121832
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发表时间：
2021-12-04
期刊：
影响因子：
4.7
通讯作者：
Castellino FJ
中科院分区：
文献类型：
--
作者：
Iwaki T;Arakawa T;Sandoval-Cooper MJ;Smith DL;Donahue D;Ploplis VA;Umemura K;Castellino FJ
纤溶系统参与了动脉粥样硬化的发生和发展。据报道，纤溶酶原（Pg）缺乏（Plg−/−）会加剧Apoe−/−小鼠动脉粥样硬化的进展。然而，Plg在低密度脂蛋白-胆固醇（LDL-C）驱动模型中发挥作用的方式尚未进行评估。为了表征Pg在LDL-C驱动模型中的作用，生成了LDL受体（LDLr）、载脂蛋白B编辑体复合物的活性组分（apobec 1）和Pg（L−/−/A−/−/Plg−/−）三重缺陷的小鼠。在缺乏Pg的情况下，动脉粥样硬化斑块的形成被严重延迟。体外研究表明，巨噬细胞对LDL的摄取被纤溶酶（Pm）增强，而相对于L-/-/A-/-小鼠，LDL的循环水平被增强，VLDL的合成被抑制。这些结果表明，在没有LDLr的情况下，脂蛋白的清除可能受到Pg/Pm的调节。结论：这项研究的结果表明，在动脉粥样硬化的LDL-C模型中，Pg加重动脉粥样硬化，并且在脂蛋白修饰和清除中也起作用。因此，控制巨噬细胞上的Pg系统以防止泡沫细胞形成将是一种新的治疗方法。
The fibrinolytic system has been implicated in the genesis and progression of atherosclerosis. It has been reported that a plasminogen (Pg) deficiency (Plg−/−) exacerbates the progression of atherosclerosis in Apoe−/− mice. However, the manner in which Plg functions in a low-density lipoprotein-cholesterol (LDL-C)-driven model has not been evaluated. To characterize the effect of Pg in an LDL-C-driven model, mice with a triple deficiency of the LDL-receptor (LDLr), along with the active component (apobec1) of the apolipoprotein B editosome complex, and Pg (L−/−/A−/−/Plg−/−), were generated. Atherosclerotic plaque formation was severely retarded in the absence of Pg. In vitro studies demonstrated that LDL uptake by macrophages was enhanced by plasmin (Pm), whereas circulating levels of LDL were enhanced, relative to L−/−/A−/− mice, and VLDL synthesis was suppressed. These results indicated that clearance of lipoproteins in the absence of LDLr may be regulated by Pg/Pm. Conclusions: The results from this study indicate that Pg exacerbates atherosclerosis in an LDL-C model of atherosclerosis and also plays a role in lipoprotein modification and clearance. Therefore, controlling the Pg system on macrophages to prevent foam cell formation would be a novel therapeutic approach.
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影响因子：
--
作者：
Bhattacharya S;Ploplis VA;Castellino FJ
通讯作者：
Castellino FJ
影响因子：
15.9
作者：
ISHIBASHI, S;BROWN, MS;HERZ, J
通讯作者：
HERZ, J
影响因子：
8.7
作者：
Klouche, M;Gottschling, S;Bhakdi, S
通讯作者：
Bhakdi, S
影响因子：
37.8
作者：
Kosaka, S;Takahashi, S;Miyamori, I
通讯作者：
Miyamori, I
影响因子：
6.7
作者：
May, AE;Schmidt, R;Klouche, M
通讯作者：
Klouche, M