Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
J Atheroscler Thromb. 2012;19(12):1110-27. doi: 10.5551/jat.13110. Epub 2012 Sep 10.
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.
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.
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 II-induced activation of Erk, and growth of cultured vascular smooth muscle cells, whereas EL expression itself did not affect cell migration or growth.
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.
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，目前尚不清楚 EL 的抑制是否对血管疾病的发生有有益影响。在这里，我们研究了 EL 对小鼠血管重构的作用。
通过结扎左颈总动脉来发展血管重构，并在 EL 基因敲除（ELKO）、EL 转基因（ELTg）和野生型（WT）小鼠之间对新生内膜病变进行组织学比较。从这些小鼠中分离 HDL，并在体外使用培养的血管平滑肌细胞评估 HDL 对细胞生长和 Erk 激活的影响。
颈动脉结扎后，ELKO 小鼠的血浆 HDL-C 水平升高 62%，ELTg 小鼠的 HDL-C 水平降低 13%。与 WT 小鼠相比，ELTg 小鼠的新生内膜病变较大，而 ELKO 小鼠的新生内膜病变较小。ELKO 小鼠的血管黏附分子表达较低，而 ETLg 小鼠的血管黏附分子表达较高。此外，ELKO 小鼠的氧化应激减轻。从 ELKO、ELTg 和 WT 小鼠中分离的 HDL 抑制了细胞间黏附分子-1 的表达、血管紧张素 II 诱导的 Erk 激活以及培养的血管平滑肌细胞的生长，而 EL 的表达本身并不影响细胞迁移或生长。
EL 的表达调节血管重构和血浆 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。
