Olson Aaron K, Protheroe Kristen N, Scholz Thomas D, Segar Jeffrey L
Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Neonatology. 2008;93(3):145-52. doi: 10.1159/000107729. Epub 2007 Sep 18.
The postnatal heart responds to biomechanical stress with hypertrophy. The fetal heart may also undergo hyperplasia, but the percentage of mitotically active cardiomyocytes decreases throughout gestation. The signaling pathways controlling growth and proliferation in the fetal heart are poorly understood.
To determine whether activation of the mitogen-activated protein kinases and Akt in the acute response to pressure loading in the fetal heart is developmentally regulated.
Pulmonary artery banding (PAB) was performed in 100- or 128-day fetuses of twin gestation (n = 6 per group) for 6 h. One twin served as a control. Right ventricular (RV) and left ventricular (LV) mitogen-activated protein kinase, Akt, and cyclin D1 protein levels were determined by Western blot.
Within each gestational age group, hemodynamic and arterial blood gas values were similar between PAB and control fetuses. The total mitogen-activated protein kinase and Akt protein levels were unchanged by PAB at both gestational ages, as were active p38 and JNK levels. The RV levels of active ERK tended to decrease in 128-day PAB fetuses as compared with controls, and LV active ERK normalized to total ERK was significantly decreased. At gestational age (GA) 100 days, RV active ERK levels were significantly higher in PAB animals as compared with controls, with a trend towards increased active Akt levels. No differences were seen in the 100-day LV. The levels of the cell cycle promoter cyclin D1 were unchanged in all animals.
Pressure loading of the fetal sheep heart leads to developmentally regulated cell signaling profiles. ERK and possibly Akt may be important regulators of in vivo cardiomyocyte hyperplasia.
出生后的心脏会通过肥大来应对生物力学应激。胎儿心脏也可能发生增生，但有丝分裂活跃的心肌细胞百分比在整个孕期都会下降。目前对控制胎儿心脏生长和增殖的信号通路了解甚少。
确定丝裂原活化蛋白激酶和Akt在胎儿心脏对压力负荷的急性反应中的激活是否受发育调控。
对双胎妊娠100天或128天的胎儿（每组n = 6）进行6小时的肺动脉环扎术（PAB）。其中一个胎儿作为对照。通过蛋白质印迹法测定右心室（RV）和左心室（LV）丝裂原活化蛋白激酶、Akt和细胞周期蛋白D1的蛋白水平。
在每个胎龄组中，PAB胎儿和对照胎儿的血流动力学和动脉血气值相似。在两个胎龄时，PAB均未改变丝裂原活化蛋白激酶和Akt的总蛋白水平，活性p38和JNK水平也未改变。与对照组相比，128天PAB胎儿的右心室活性ERK水平有下降趋势，左心室活性ERK与总ERK的比值显著降低。在100天胎龄时，与对照组相比，PAB动物的右心室活性ERK水平显著升高，活性Akt水平有升高趋势。100天的左心室未见差异。所有动物的细胞周期促进因子细胞周期蛋白D1水平均未改变。
胎儿绵羊心脏的压力负荷导致细胞信号转导谱受发育调控。ERK以及可能的Akt可能是体内心肌细胞增生的重要调节因子。
