Influence of gestational overfeeding on cardiac morphometry and hypertrophic protein markers in fetal sheep.
Influence of gestational overfeeding on cardiac morphometry and hypertrophic protein markers in fetal sheep.
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DOI：
10.1016/j.jnutbio.2009.11.006
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发表时间：
2011-01
影响因子：
5.6
通讯作者：
Ren, Jun
中科院分区：
文献类型：
--
作者：
Fan, Xiujuan;Turdi, Subat;Ford, Stephen P.;Hua, Yinan;Nijland, Mark J.;Zhu, Meijun;Nathanielsz, Peter W.;Ren, Jun
子宫内营养过剩与成年期心血管疾病的发生有关，但其潜在机制尚不清楚。本研究评估了母亲营养过剩对胎儿心脏形态和肥大相关mRNA/蛋白表达的影响。从交配前60天至妊娠第75天（D 75），对经产母羊饲喂150%的NRC营养需求量（过饲组）或100%的NRC营养需求量（对照组）。观察心脏形态学、组织学及Akt、Foxo 3a、糖原合成酶激酶3β、mTOR、NFATc 3、GATA 4、心钠素、钙调神经磷酸酶A和caspase-8的表达。D 75营养过剩胎儿的冠臀长、左、右心室游离壁重量和左心室壁厚度增加。H&E染色显示过度喂养组心肌组织中肌纤维排列不规则，间质间隙增大。Masson三色染色显示过度喂养组心肌组织肌纤维肥大，肌束排列紊乱。过度喂养显著增强了两个心室中Foxo 3a的磷酸化，而两个心室中Akt、Foxo 3a、GSK 3 β和caspase-8以及磷酸化Akt和GSK 3 β的蛋白表达不受影响。过度喂养增加了左心室mTOR、NFATc 3（总的和磷酸化的）和钙调神经磷酸酶A。GATA 4、pGATA 4和ANF表达在两个心室中无变化。总的来说，我们的数据表明，在妊娠早期至中期（D 75）过度喂养导致形态学变化，而没有明显的病理学，这可能与mTOR，NFATc 3，钙调神经磷酸酶A的表达升高和Foxo 3a，mTOR和NFATc 3的磷酸化有关。
Intrauterine overnutrition is associated with development of cardiovascular disease in adulthood although the underlying mechanism has not been precisely elucidated. This study evaluated the effects of maternal overnutrition on fetal cardiac morphometry and hypertrophy-related mRNA/protein expression. Multiparous ewes were fed either 150% of NRC nutrient requirements (overfed group) or 100% of NRC requirements (control group) from 60 days before mating to day 75 (D75) of gestation, when ewes were euthanized. Cardiac morphometry, histology and expression of Akt, forkhead-3a (Foxo3a), glycogen synthase kinase-3β (GSK3β), mammalian target of rapamycin (mTOR), NFATc3 and GATA4, atrial natriuretic factor (ANF), calcineurin A and caspase-8 were examined. Crown rump length, left and right ventricular free wall weights and left ventricular wall thickness were increased in D75 overnourished fetuses. H&E staining revealed irregular myofiber orientation and increased interstitial space in heart tissues from overfed group. Masson’s trichrome staining displayed myofiber hypertrophy and fascicular disarray in heart tissues from overfed group. Overfeeding significantly enhanced Foxo3a phosphorylation in both ventricles while protein expression of Akt, Foxo3a, GSK3β and caspase-8 as well as phosphorylated Akt and GSK3β in either ventricle was unaffected. Overfeeding increased left ventricular mTOR, NFATc3 (both total and phosphorylated) and calcineurin A. GATA4, pGATA4 and ANF expression were unchanged in both ventricles. Collectively, our data suggested that overfeeding during early to mid gestation (D75) leads to morphometric changes without overt pathology which may be related to elevated expression of mTOR, NFATc3, calcineurin A and phosphorylation of Foxo3a, mTOR and NFATc3.
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DOI：
10.1073/pnas.072647999
发表时间：
2002-04-02
影响因子：
11.1
作者：
Bueno, OF;Wilkins, BJ;Molkentin, JD
通讯作者：
Molkentin, JD
影响因子：
7.8
作者：
Haq, S;Choukroun, G;Kang, Z B;Ranu, H;Matsui, T;Rosenzweig, A;Molkentin, J D;Alessandrini, A;Woodgett, J;Hajjar, R;Michael, A;Force, T
通讯作者：
Force, T
DOI：
10.1073/pnas.162100799
发表时间：
2002-08-20
影响因子：
11.1
作者：
Fiedler, B;Lohmann, SM;Wollert, KC
通讯作者：
Wollert, KC
影响因子：
2.5
作者：
NATHANIELSZ, PW
通讯作者：
NATHANIELSZ, PW
影响因子：
4.8
作者：
Cameron, VA;Rademaker, MT;Richards, AM
通讯作者：
Richards, AM