Fatty acid translocase/CD36 deficiency does not energetically or functionally compromise hearts before or after ischemia
Fatty acid translocase/CD36 deficiency does not energetically or functionally compromise hearts before or after ischemia
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DOI：
10.1161/01.cir.0000121730.41801.12
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发表时间：
2004-03-30
期刊：
影响因子：
37.8
通讯作者：
Dyck, JRB
中科院分区：
文献类型：
--
作者：
Kuang, M;Febbraio, M;Dyck, JRB
背景 - 来自人类的证据表明，脂肪酸移位酶 (FAT)/CD36 缺乏可导致心脏功能和/或能量受损，但数据不明确，而且该主题仍存在争议。在本报告中，我们评估了 FAT/CD36 对完整心脏中总体脂肪酸氧化率的贡献，并确定了 FAT/CD36 对缺血心脏再灌注期间能量代谢的影响。方法和结果 - 用含有 0.4 或 1.2 mmol/L [U-H-3] 棕榈酸酯的 Krebs-Henseleit 溶液灌注来自野生型和 FAT/CD36 敲除 (KO) 小鼠的分离工作心脏，5 mmol/L [U-C-14]葡萄糖、2.5 mmol/L 钙和 100 muU/mL 胰岛素，前负荷压力为 11.5 mm Hg，后负荷压力为 50 mm Hg。心脏有氧灌注30分钟或有氧灌注30分钟，然后进行18分钟的整体无血流缺血和40分钟的有氧再灌注。在两种棕榈酸盐浓度（0.4 或 1.2 mmol/L）下，FAT/CD36-KO 心脏中的脂肪酸氧化率均显着低于野生型心脏。此外，FAT/CD36-KO小鼠的心脏显示出葡萄糖氧化率的代偿性增加。在缺血后的有氧再灌注中，FAT/CD36-KO心脏的心脏工作恢复到与野生型心脏相同的程度。结论——FAT/CD36缺陷的心脏在能量或功能上没有受到损害，并且对缺血性损伤并不更敏感，因为葡萄糖氧化可以补偿脂肪酸衍生的ATP的损失。
Background - Evidence from humans suggests that fatty acid translocase (FAT)/CD36 deficiency can lead to functionally and/or energetically compromised hearts, but the data are equivocal, and the subject remains controversial. In this report we assessed the contribution of FAT/CD36 to overall fatty acid oxidation rates in the intact heart and determined the effect of FAT/CD36 on energy metabolism during reperfusion of ischemic hearts.Methods and Results - Isolated working hearts from wild-type and FAT/CD36-knockout (KO) mice were perfused with Krebs-Henseleit solution containing 0.4 or 1.2 mmol/L [U-H-3]palmitate, 5 mmol/L [U-C-14]glucose, 2.5 mmol/L calcium, and 100 muU/mL insulin at a preload pressure of 11.5 mm Hg and afterload pressure of 50 mm Hg. Hearts were aerobically perfused for 30 minutes or aerobically perfused for 30 minutes, followed by 18 minutes of global no-flow ischemia and 40 minutes of aerobic reperfusion. Rates of fatty acid oxidation in FAT/CD36-KO hearts were significantly lower than in wild-type hearts at both concentrations of palmitate (0.4 or 1.2 mmol/L). In addition, hearts from FAT/CD36-KO mice displayed a compensatory increase in glucose oxidation rates. On aerobic reperfusion after ischemia, cardiac work of FAT/CD36-KO hearts recovered to the same extent as wild-type hearts.Conclusions - FAT/CD36-deficient hearts are not energetically or functionally compromised and are not more sensitive to ischemic injury because glucose oxidation can compensate for the loss of fatty acid - derived ATP.