Placental Insufficiency Alters Fetal Cardiac Growth

胎盘功能不全似乎是胎儿发育不良的重要原因，在以下情况下 先兆子痫到不对称性胎儿宫内发育迟缓。胎儿生长不良与一种 显著增加成人发病冠状动脉疾病的风险。最近的数据显示，低足月出生体重 也与室壁增厚和冠状动脉内径缩小有关。很可能是 在动脉压升高的情况下，未发育成熟的心脏将更不能执行收缩功 出生时，它可能不能在出生后产生正常的心肌细胞补充。如果 胎儿的心脏在胎盘功能不全加上高血压的情况下发育，它有 额外的问题。我们假设它会增加心肌细胞的数量，但也会过早地 将细胞分配到终末分化途径，出生后将不能再生细胞。这个 结果将是出生后心脏肥大，细胞较大但较少。这样的心，如图所示 对于出生前低氧的成年大鼠，毛细血管网络会更小，更少，但更大 过度劳累的心肌细胞将更容易患上冠心病和心力衰竭。我们 假设胎盘病理导致低氧血症和糖皮质激素(皮质醇)过多，然后 心脏病理学。过量的皮质醇与盐皮质激素受体结合，导致顺应性丧失 通过纤维化，降低收缩能力，阻碍冠状动脉生长。保护伞假说： 在胎儿胎盘栓塞术中，胎儿心肌的生长和发育模式如下 由心脏发育所产生的血流动力学和皮质类固醇环境决定。我们 将通过4个目标来检验这一前提。 目的1：研究胎盘条件下心肌细胞的生长和成熟模式 在反应性高血压程度不同的两组中。 目的2：确定胎盘条件下心脏发育的功能特征 不够用。 目的3：探讨皮质类固醇激素对心肌细胞生长发育的调节作用。 目的4：确定胎盘条件下发育的心脏的出生后生长模式 不够用。

Placental insufficiency appears to be an important cause of fetal undergrowth in conditions ranging from preeclampsia to asymmetrical intrauterine growth retardation. Fetal undergrowth is associated with a significantly increased risk adult onset coronary artery disease. Recent data show that low term birthweight is also associated with ventricular wall thickening and a reduction in coronary artery diameter. It is likely that the undergrown heart will be less able to perform systolic work in the face of increased arterial pressures at birth and it may not be able to generate a normal complement of cardiomyocytes during postnatal life. If the heart of a fetus develops under the conditions of placental insufficiency plus hypertension, it has an additional problem. We hypothesize that it will increase its myocyte numbers but will also prematurely allocate cells to the terminal differentiation pathway and will not be able to regenerate cells after birth. The outcome will be a hypertrophied heart with larger but fewer cells during postnatal life. Such hearts, as shown for adult rats that were hypoxemic before birth, will have a smaller capillary network, fewer but larger overworked cardiomyocytesand will be more vulnerable to coronary disease and heart failure. We hypothesize that placental pathology leads to hypoxemia and glucocorticoid (cortisol) excess and then to heart pathology. Excess cortisol binds the mineralocorticoid receptor-- which leads to loss of compliance through fibrosis, decreases contractility, and stunts coronary arterial growth. Umbrella hypothesis: the patterns of growth and development of the fetal myocardium, during a fetal placental embolization, are determined by the resulting hemodynamic and corticosteroid environment in which the heart develops. We will test this premise through 4 aims. Aim 1: To characterize the patterns of cardiomyocytegrowth and maturation under conditions of placental insufficiency in two groups that differ by their degree of reactive hypertension. Aim 2: To determine the functional characteristics of hearts developing under conditions of placental insufficiency. Aim 3: To determine roles of corticosteroid hormones in regulating myocyte growth and development. Aim 4: To determine postnatal growth patterns of hearts that developed under conditions of placental insufficiency.