IUGR decreases cardiomyocyte endowment and alters cardiac metabolism in a sex- and cause-of-IUGR-specific manner
IUGR decreases cardiomyocyte endowment and alters cardiac metabolism in a sex- and cause-of-IUGR-specific manner
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DOI：
10.1152/ajpregu.00180.2017
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发表时间：
2018-07-01
影响因子：
2.8
通讯作者：
Morrison, J. L.
中科院分区：
文献类型：
--
作者：
Botting, K. J.;Loke, X. Y.;Morrison, J. L.
胎儿宫内生长受限(IUGR)会增加成年后罹患缺血性心脏病的风险。对大鼠的研究表明，在宫内暴露于低氧环境的雄性和后代中，心脏的脆弱性更明显。因此，我们的目的是检验假设：1)IUGR青春期男性，而不是女性，与对照组相比，心肌细胞较少，心脏代谢基因表达改变；以及2)由于低氧引起的IUGR与由于营养限制导致的IUGR相比，对这些参数的影响更大。在妊娠后半程，用低氧(MH；10%O-2，n=9)或营养限制(MNR，相当于减少摄食量30%，n=9)诱导豚鼠IUGR，并与对照组(n=11)比较。120日龄处死动物，固定左心室血流灌注量，分别用定量RT-PCR和Western blotting测定心肌细胞数量和冻存心肌代谢相关基因和蛋白的丰度。MH减少了女性的心肌细胞数量(P<；0.05)，但没有减少男性或MNR的青少年后代的心肌细胞数量。此外，IUGR雄鼠肌浆中负责脂肪酸活化的基因(FACS)和转运到线粒体的基因(AMPK-a(2)和ACC；P<；0.05)的表达减少，而接触MH的雌鼠AMP激活的蛋白激酶-α的激活/磷酸化增加(P<；0.05)。我们推测，本研究中观察到的心肌细胞天赋和心脏基因表达的变化是宫内编程的直接结果。由于子女在这个年龄段没有患肥胖症、高血压。或左心室肥厚。
Intrauterine growth restriction (IUGR) increases the risk of ischemic heart disease in adulthood. Studies in rats suggest cardiac vulnerability is more pronounced in males and in offspring that were exposed to hypoxia in utero. Therefore, we aimed to test the hypotheses that 1) IUGR adolescent males, but not females, have fewer cardiomyocytes and altered expression of cardiometabolic genes compared with controls; and 2) IUGR due to hypoxia has a greater effect on these parameters compared with IUGR due to nutrient restriction. IUGR was induced in guinea pigs by maternal hypoxia (MH; 10% O-2, n = 9) or maternal nutrient restriction (MNR; similar to 30% reduction in food intake, n = 9) in the second half of pregnancy and compared with control (n = 11). At 120 days of age, postmortem was performed and the left ventricle perfusion fixed for stereological determination of cardiomyocyte number or snap frozen to determine the abundance of cardiometabolic genes and proteins by quantitative RT-PCR and Western blotting, respectively. MH reduced the number of cardiomyocytes in female (P < 0.05), but not male or MNR, adolescent offspring. Furthermore, IUGR males had decreased expression of genes responsible for fatty acid activation in the sarcoplasm (FACS) and transport into the mitochondria (AMPK-a(2) and ACC; P < 0.05) and females exposed to MH had increased activation/phosphorylation of AMP-activated protein kinase-alpha (P < 0.05). We postulate that the changes in cardiomyocyte endowment and cardiac gene expression observed in the present study are a direct result of in utero programming. as offspring at this age did not suffer from obesity, hypertension. or left ventricular hypertrophy.