Overexpression of Prolyl-4-Hydroxylase-α1 Stabilizes but Increases Shear Stress-Induced Atherosclerotic Plaque in Apolipoprotein E-Deficient Mice.
Overexpression of Prolyl-4-Hydroxylase-α1 Stabilizes but Increases Shear Stress-Induced Atherosclerotic Plaque in Apolipoprotein E-Deficient Mice.
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Prolyl-4-Hydroxylase-alpha1 的过度表达可稳定但增加载脂蛋白 E 缺陷小鼠中剪切应力诱导的动脉粥样硬化斑块。
DOI：
10.1155/2016/1701637
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Cao XQ;Liu XX;Li MM;Zhang Y;Chen L;Wang L;Di MX;Zhang M
动脉粥样硬化斑块的破裂和侵蚀可诱发冠状动脉血栓形成。脯氨酰-4-羟化酶（P4 H）在所有已知类型的胶原的合成中起核心作用，胶原是动脉粥样硬化斑块中细胞外基质的最丰富的成分。动脉粥样硬化的发病机制被认为部分是由剪切应力引起的。本研究旨在探讨P4 H α1与剪切应力诱导的动脉粥样硬化斑块的关系。通过放置剪切应力管型，将ApoE−/−小鼠的颈动脉暴露于低剪切应力和振荡剪切应力条件下2周;我们将60只雄性ApoE−/−小鼠分为3组，分别接受生理盐水（模拟）（n = 20）、空慢病毒（lenti-EGFP）（n = 20）和慢病毒-P4 H α1（lenti-P4 H α1）（n = 20）治疗。我们的研究结果表明，在lenti-P4 H α1治疗2周后，低切应力和振荡切应力诱导的斑块增加了胶原和纤维帽厚度，减少了巨噬细胞积聚，但没有改变脂质积聚。我们还观察到P4 Ha 1的过表达增加了斑块的大小。提示P4 H α1过表达可能是稳定易损斑块的潜在治疗靶点。
The rupture and erosion of atherosclerotic plaque can induce coronary thrombosis. Prolyl-4-hydroxylase (P4H) plays a central role in the synthesis of all known types of collagens, which are the most abundant constituent of the extracellular matrix in atherosclerotic plaque. The pathogenesis of atherosclerosis is thought to be in part caused by shear stress. In this study, we aimed to investigate a relationship between P4Hα1 and shear stress-induced atherosclerotic plaque. Carotid arteries of ApoE−/− mice were exposed to low and oscillatory shear stress conditions by the placement of a shear stress cast for 2 weeks; we divided 60 male ApoE−/− mice into three groups for treatments with saline (mock) (n = 20), empty lentivirus (lenti-EGFP) (n = 20), and lentivirus-P4Hα1 (lenti-P4Hα1) (n = 20). Our results reveal that after 2 weeks of lenti-P4Hα1 treatment both low and oscillatory shear stress-induced plaques increased collagen and the thickness of fibrous cap and decreased macrophage accumulation but no change in lipid accumulation. We also observed that overexpression of P4Ha1 increased plaque size. Our study suggests that P4Hα1 overexpression might be a potential therapeutic target in stabilizing vulnerable plaques.
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影响因子：
64.5
作者：
Moore KJ;Tabas I
通讯作者：
Tabas I
影响因子：
15.9
作者：
Seimon, Tracie A.;Wang, Yibin;Tabas, Ira A.
通讯作者：
Tabas, Ira A.
DOI：
10.1038/nri3520
发表时间：
2013-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
20.1
作者：
Ichii, T;Koyama, H;Nishizawa, Y
通讯作者：
Nishizawa, Y
DOI：
10.1161/01.atv.11.5.1223
发表时间：
1991-09-01
期刊：
ARTERIOSCLEROSIS AND THROMBOSIS
影响因子：
--
作者：
AMENTO, EP;EHSANI, N;LIBBY, P
通讯作者：
LIBBY, P