Absence of fatty acid transporter CD36 protects against Western-type diet-related cardiac dysfunction following pressure overload in mice.
Absence of fatty acid transporter CD36 protects against Western-type diet-related cardiac dysfunction following pressure overload in mice.
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脂肪酸转运蛋白 CD36 的缺失可防止小鼠压力超负荷后出现西式饮食相关的心脏功能障碍。
DOI：
10.1152/ajpendo.00106.2011
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
M. Diamant
中科院分区：
文献类型：
--
作者：
Laura K. M. Steinbusch;J. Luiken;R. Vlasblom;A. Chabowski;Nicole T. H. Hoebers;W. Coumans;I. Vroegrijk;P. Voshol;D. M. Ouwens;J. F. Glatz;M. Diamant
心脏病患者通常是肥胖和高血压，但在大多数研究中，这些条件是分开调查的。在这里，我们的目的是1）阐明代谢和机械物理应激在小鼠心功能障碍发展中的相互作用，2）通过消融脂肪酸转运蛋白CD 36来预防这种相互作用。雄性野生型（WT）C57 Bl/6小鼠和CD 36（-/-）小鼠接受食物或西式饮食（WTD）10周，然后在麻醉下进行假手术或横向主动脉缩窄（TAC）。连续6周的饮食后，心脏功能，形态，血脂和分子参数进行了评估。WTD给药影响WT和CD 36（-/-）小鼠的体重和器官重量，但仅影响WT小鼠的血糖和胰岛素浓度。在接受WTD的WT小鼠中，心脏脂质浓度增加，在食物中CD 36（-/-）降低，并且在接受WTD的CD 36（-/-）中保持不变。TAC诱导WT小鼠的心脏肥大，但不影响心脏功能和心脏脂质浓度。WTD或CD 36消融使TAC的结局恶化。消融CD 36可防止TAC引起的WTD相关的心脏功能和结构变化恶化。总之，当心脏同时受到代谢和机械物理两种压力时，心脏功能障碍和重塑会恶化。CD 36消融可预防WTD导致的代谢应激。因此，代谢条件是受损心脏的关键因素，并为心脏保护中的代谢操纵提供了新的靶点。
Cardiac patients often are obese and have hypertension, but in most studies these conditions are investigated separately. Here, we aimed at 1) elucidating the interaction of metabolic and mechanophysical stress in the development of cardiac dysfunction in mice and 2) preventing this interaction by ablation of the fatty acid transporter CD36. Male wild-type (WT) C57Bl/6 mice and CD36(-/-) mice received chow or Western-type diet (WTD) for 10 wk and then underwent a sham surgery or transverse aortic constriction (TAC) under anesthesia. After a 6-wk continuation of the diet, cardiac function, morphology, lipid profiles, and molecular parameters were assessed. WTD administration affected body and organ weights of WT and CD36(-/-) mice, but it affected only plasma glucose and insulin concentrations in WT mice. Cardiac lipid concentrations increased in WT mice receiving WTD, decreased in CD36(-/-) on chow, and remained unchanged in CD36(-/-) receiving WTD. TAC induced cardiac hypertrophy in WT mice on chow but did not affect cardiac function and cardiac lipid concentrations. WTD or CD36 ablation worsened the outcome of TAC. Ablation of CD36 protected against the WTD-related aggravation of cardiac functional and structural changes induced by TAC. In conclusion, cardiac dysfunction and remodeling worsen when the heart is exposed to two stresses, metabolic and mechanophysical, at the same time. CD36 ablation prevents the metabolic stress resulting from a WTD. Thus, metabolic conditions are a critical factor for the compromised heart and provide new targets for metabolic manipulation in cardioprotection.
影响因子：
15.9
作者：
Takeda, Norifumi;Manabe, Ichiro;Nagai, Ryozo
通讯作者：
Nagai, Ryozo
DOI：
10.1152/ajpheart.00108.2003
发表时间：
2003-09-01
影响因子：
4.8
作者：
Hu, P;Zhang, DF;Litwin, SE
通讯作者：
Litwin, SE
影响因子：
25.7
作者：
Shiri-Sverdlov, R;Wouters, K;Hofker, MH
通讯作者：
Hofker, MH