Expression of Endothelial Lipase Correlates with the Size of Neointima in a Murine Model of Vascular Remodeling
Expression of Endothelial Lipase Correlates with the Size of Neointima in a Murine Model of Vascular Remodeling
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DOI：
10.5551/jat.13110
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发表时间：
2012-01-01
影响因子：
4.4
通讯作者：
Hirata, Ken-ichi
中科院分区：
文献类型：
--
作者：
Sun, Li;Ishida, Tatsuro;Hirata, Ken-ichi
目的：内皮脂肪酶 (EL) 通过促进 HDL 分解代谢来调节血浆高密度脂蛋白胆固醇 (HDL-C) 水平。然而，抑制 EL 是否对血管疾病的发生具有有益作用仍不清楚。在这里，我们研究了 EL 对小鼠血管重塑的作用。 方法：通过结扎左颈总动脉进行血管重塑，并对 EL 敲除 (ELKO)、EL 转基因 (ELTg) 和野生型 (WT) 小鼠的新内膜病变进行组织学比较。从这些小鼠中分离出 HDL，并使用培养的血管平滑肌细胞在体外评估 HDL 对细胞生长和 Erk 激活的影响。 结果：颈动脉结扎后，与 WT 小鼠相比，ELKO 小鼠血浆 HDL-C 水平高出 62%，ELTg 小鼠血浆 HDL-C 水平低 13%。与 WT 小鼠相比，ELTg 小鼠的新内膜病变尺寸明显更大，而 ELKO 小鼠的新内膜病变尺寸明显更小。与WT小鼠相比，ELKO小鼠中粘附分子的血管表达较低，而ELTg小鼠中粘附分子的血管表达较高。此外，ELKO 小鼠的氧化应激得到缓解。从 ELKO、ELTg 和 WT 小鼠中分离的 HDL 抑制细胞间粘附分子 1 的表达、血管紧张素诱导的 Erk 激活以及培养的血管平滑肌细胞的生长，而 EL 表达本身不影响细胞迁移或生长。 结论：EL 表达调节血管重塑以及血浆 HDL-C 水平。 EL 失活可能会增加 HDL 颗粒，从而抑制平滑肌细胞的生长和迁移。动脉粥样硬化血栓杂志，2012； 19：1110-1127。
Aim: Endothelial lipase (EL) regulates plasma high-density lipoprotein-cholesterol (HDL-C) levels by promoting HDL catabolism. However, it remains unknown whether the inhibition of EL has beneficial effects on the genesis of vascular diseases. Here, we investigated the role of EL on vascular remodeling in mice.Methods: Vascular remodeling was developed by ligation of the left common carotid artery and neointimal lesions were histologically compared between EL-knockout (ELKO), EL-transgenic (ELTg), and wild-type (WT) mice. HDL was isolated from these mice, and effects of the HDL on cell growth and Erk activation were evaluated in vitro using cultured vascular smooth muscle cells.Results: Plasma HDL-C levels were 62% higher in ELKO and 13% lower in ELTg than in WT mice, after the carotid ligation. The size of neointimal lesion was significantly larger in ELTg and smaller in ELKO than in WT mice. Vascular expression of adhesion molecules was lower in ELKO and higher in ELTg compared with WT mice. Moreover, oxidative stress was attenuated in ELKO mice. HDL isolated from ELKO, ELTg, and WT mice inhibited expression of intercellular adhesion molecule-1, angiotensin.-induced activation of Erk, and growth of cultured vascular smooth muscle cells, whereas EL expression itself did not affect cell migration or growth.Conclusion: EL expression modulates vascular remodeling as well as plasma HDL-C levels. EL inactivation may increase HDL particles that can inhibit smooth muscle cell growth and migration. J Atheroscler Thromb, 2012; 19:1110-1127.