Leptin regulates neointima formation after arterial injury through mechanisms independent of blood pressure and the leptin receptor/STAT3 signaling pathways involved in energy balance
Leptin regulates neointima formation after arterial injury through mechanisms independent of blood pressure and the leptin receptor/STAT3 signaling pathways involved in energy balance
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DOI：
10.1161/01.atv.0000252068.89775.ee
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发表时间：
2007-01-01
影响因子：
8.7
通讯作者：
Eitzman, Daniel T.
中科院分区：
文献类型：
--
作者：
Bodary, Peter F.;Shen, Yuechun;Eitzman, Daniel T.
瘦素是一种脂肪细胞源性激素，对能量平衡至关重要，并与血管疾病过程有关。相关的细胞瘦素受体池和信号通路参与瘦素相关的血管phenotypesinvivo.Methods和结果动脉损伤诱导野生型（WT），瘦素缺乏（lep（ob/ob）），瘦素受体缺乏（lepr（db/db））小鼠。与野生型小鼠相比，lep（ob/ob）和lepr（db/db）小鼠的新生内膜的形成受到保护。WT和lepr（db/db）小鼠间的骨髓移植实验表明lepr（db/db）小鼠的血管保护作用不归因于骨髓衍生成分上瘦素受体表达的缺乏。为了研究lepr介导的信号转导子和转录激活子3（STAT 3）信号通路在血管损伤反应中的作用，lepr（s/s）小鼠在STAT 3信号通路中瘦素受体缺陷的纯合子经历股动脉损伤。尽管相似的肥胖和血压水平，在lepr（s/s）小鼠的新生内膜面积显着增加lepr（db/db）mice.Conclusions相比，瘦素受体介导的新生内膜形成和血管平滑肌细胞增殖的分子机制在很大程度上是独立的STAT 3依赖的信号通路参与能量平衡。
Background - Leptin is an adipocyte-derived hormone critical for energy homeostasis and implicated in vascular disease processes. The relevant cellular leptin receptor pools and signaling pathways involved in leptin-related vascular phenotypes in vivo are unclear.Methods and Results - Arterial injury was induced in wild-type (wt), leptin-deficient (lep(ob/ob)), and leptin receptor deficient (lepr(db/db)) mice. Compared with wt mice, lep(ob/ob) and lepr(db/db) mice were protected from the development of neointima. Bone marrow transplantation experiments between wt and lepr(db/db) mice indicated that the vascular protection in lepr(db/db) mice was not attributable to lack of leptin receptor expression on bone marrow - derived elements. To investigate the role of the lepr-mediated signal transducer and activator of transcription 3 (STAT3) signaling pathway in the response to vascular injury, lepr(s/s) mice homozygous for a leptin receptor defective in STAT3 signaling underwent femoral arterial injury. Despite similar obesity and blood pressure levels, the neointimal area in lepr(s/s) mice was significantly increased compared with lepr(db/db) mice.Conclusions - The molecular mechanism by which the leptin receptor mediates neointima formation and vascular smooth muscle cell proliferation is largely independent of the STAT3-dependent signaling pathways involved in energy balance.