The Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan.
Life Sci. 2010 Feb 27;86(9-10):365-71. doi: 10.1016/j.lfs.2010.01.007. Epub 2010 Jan 21.
FHL2, a member of the four and a half LIM domain (FHL) family of proteins, may play an important role in the circulatory system and in particular atherosclerosis.
To investigate the role of FHL2 in atherogenesis, FHL2-null and wild-type control male mice were fed either a normal chow (NC) or a cholesterol-enriched diet (CED).
At 3 months post CED, aortic atherosclerotic plaques were observed in both control and FHL2-null mice. Lesions in control mice increased dramatically by 6 months of CED. In contrast, lesion size did not increase during this time in CED-fed FHL2-null mice. Relative to control mice on a normal chow of diet (NCD), control mice on a CED exhibited lower circulating nitric oxide (NO) levels, and decreased expression of connexin37 (Cx37) and Cx40 in aortic endothelium. In contrast, FHL2-null mice on a CED maintained similar levels of circulating NO as FHL2-null mice fed a NCD. Cxs levels in aortic endothelium of FHL2-null mutants on a NCD were lower relative to control mice on a NCD, and did not decrease with CED.
Our data demonstrate a role for FHL2 in atherogenesis, the regulation of circular NO release, and expression of gap junctions within aortic endothelium.
FHL2 是四个半 LIM 结构域（FHL）蛋白家族的成员，可能在循环系统中发挥重要作用，尤其是在动脉粥样硬化中。
为了研究 FHL2 在动脉粥样硬化形成中的作用，FHL2 缺失和野生型对照雄性小鼠分别喂食正常饮食（NC）或富含胆固醇的饮食（CED）。
在 CED 后 3 个月，在对照和 FHL2 缺失小鼠中均观察到主动脉粥样硬化斑块。在 6 个月的 CED 中，对照小鼠的病变显著增加。相比之下，在这段时间内，CED 喂养的 FHL2 缺失小鼠的病变大小没有增加。与正常饮食（NCD）喂养的对照小鼠相比，CED 喂养的对照小鼠的循环一氧化氮（NO）水平较低，主动脉内皮中的连接蛋白 37（Cx37）和 Cx40 表达减少。相比之下，CED 喂养的 FHL2 缺失小鼠保持与 FHL2 缺失小鼠喂食 NCD 相似的循环 NO 水平。NCD 喂养的 FHL2 缺失突变体的主动脉内皮 Cxs 水平低于对照小鼠的 NCD，并且随着 CED 不减少。
我们的数据表明 FHL2 在动脉粥样硬化形成、循环 NO 释放的调节以及主动脉内皮中间隙连接的表达中起作用。
