Changes in cardiac lipid metabolism during sepsis: The essential role of very low-density lipoprotein receptors
Changes in cardiac lipid metabolism during sepsis: The essential role of very low-density lipoprotein receptors
复制标题
DOI：
10.1016/j.cardiores.2005.11.014
复制
发表时间：
2006-02-01
影响因子：
10.8
通讯作者：
Ikeda, U
中科院分区：
文献类型：
--
作者：
Jia, LJ;Takahashi, M;Ikeda, U
目的：脓毒症伴随着心肌功能障碍和心脏代谢的动态改变。我们最近证明，极低密度脂蛋白受体（VLDL-R），这是丰富的表达在心脏中，在空腹心脏的能量代谢中起着关键作用。然而，很少有人知道的功能和调节的VLDL-R在脓毒症。在本研究中，我们探讨了脂多糖（LPS）刺激的心脏在体内的脂质积累和VLDL-R的表达和调节VLDL-R的表达在vitro.Methods和结果：电子显微镜和免疫组化表明，LPS显着降低脂质积累和VLDL-R的表达在禁食小鼠的心脏。LPS处理还下调新生大鼠心肌细胞VLDL-R，这种下调可被白细胞介素（IL）-1 β受体拮抗剂完全逆转。IL-1 β以时间和剂量依赖性方式下调VLDL-R的表达，并显著降低DiI标记的β-VLDL的摄取，但不降低DiI标记的低密度脂蛋白（LDL）的摄取。使用特定的药理学抑制剂和短的干扰RNA显示，热休克蛋白90所需的IL-1 β下调VLDL-R expression.Conclusions：这些研究结果表明，IL-1 β是一个主要的调解人的变化，在心脏的脂质和能量代谢在脓毒症通过下调心肌VLDL-R的表达。(C)2005年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Objective: Sepsis accompanies myocardial dysfunction and dynamic alterations of cardiac metabolism. We have recently demonstrated that the very low-density lipoprotein receptor (VLDL-R), which is abundantly expressed in the heart, plays a key role in energy metabolism of the fasting heart. However, little is known about the function and regulation of the VLDL-R during sepsis. In the present study, we explored lipid accumulation and VLDL-R expression in the lipopolysaccharide (LPS)-stimulated heart in vivo and regulation of VLDL-R expression in vitro.Methods and results: Electron microscopy and immunohistochemistry demonstrated that LPS significantly decreased both lipid accumulation and VLDL-R expression in the hearts of fasting mice. Treatment with LPS also downregulated VLDL-R in rat neonatal cardiac myocytes, and this downregulation was completely reversed by interleukin (IL)-1 beta receptor antagonist. IL-1 beta downregulated the expression of VLDL-R in a time- and dose-dependent manner and markedly reduced the uptake of DiI-labeled beta-VLDL but not DiI-labeled low-density lipoprotein (LDL). Use of specific pharmacologic inhibitors and short interference RNA revealed that Hsp90 was required for IL-1 beta to downregulate VLDL-R expression.Conclusions: These findings suggest that IL-1 beta is a principle mediator of changes in cardiac lipid and energy metabolism during sepsis through the downregulation of myocardial VLDL-R expression. (C) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.