UQ Centre for Clinical Research, Faculty of Medicine, University of Queensland, Brisbane 4029, Australia.
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Cells. 2022 Feb 21;11(4):742. doi: 10.3390/cells11040742.
Mediators of cardiac injury in preeclampsia are not well understood. Preeclamptic women have decreased cardiac global longitudinal strain (GLS), a sensitive measure of systolic function that indicates fibrosis and tissue injury. GLS is worse in preeclampsia compared to gestational hypertension, despite comparable blood pressure, suggesting that placental factors may be involved. We previously showed that Activin A, a pro-fibrotic factor produced in excess by the placenta in preeclampsia, predicts impaired GLS postpartum. Here, we hypothesized that chronic excess levels of Activin A during pregnancy induces cardiac dysfunction. Rats were assigned to sham or activin A infusion (1.25-6 µg/day) on a gestational day (GD) 14 ( = 6-10/group). All animals underwent blood pressure measurement and comprehensive echocardiography followed by euthanasia and the collection of tissue samples on GD 19. Increased circulating activin A (sham: 0.59 ± 0.05 ng/mL, 6 µg/day: 2.8 ± 0.41 ng/mL, < 0.01) was associated with impaired GLS (Sham: -22.1 ± 0.8%, 6 µg/day: -14.7 ± 1.14%, < 0.01). Activin A infusion (6 µg/day) increased beta-myosin heavy chain expression in heart tissue, indicating cardiac injury. In summary, our findings indicate that increasing levels of activin A during pregnancy induces cardiac dysfunction and supports the concept that activin A may serve as a possible mediator of PE-induced cardiac dysfunction.
先兆子痫中心脏损伤的介质尚不清楚。先兆子痫妇女的心脏整体纵向应变（GLS）降低，这是一种敏感的收缩功能测量指标，表明存在纤维化和组织损伤。与妊娠期高血压相比，先兆子痫患者的 GLS 更差，尽管血压相当，这表明胎盘因素可能参与其中。我们之前表明，激活素 A 是一种在先兆子痫中由胎盘过度产生的促纤维化因子，可预测产后 GLS 受损。在这里，我们假设怀孕期间慢性过量的激活素 A 会引起心脏功能障碍。大鼠被分配到假手术或激活素 A 输注（1.25-6 µg/天）组，于妊娠第 14 天（= 6-10/组）开始。所有动物均进行血压测量和全面超声心动图检查，然后在妊娠第 19 天安乐死并收集组织样本。循环激活素 A 水平升高（假手术组：0.59 ± 0.05ng/mL，6 µg/天组：2.8 ± 0.41ng/mL， < 0.01）与 GLS 降低相关（假手术组：-22.1 ± 0.8%，6 µg/天组：-14.7 ± 1.14%， < 0.01）。激活素 A 输注（6 µg/天）增加了心脏组织中β-肌球蛋白重链的表达，表明存在心脏损伤。总之，我们的研究结果表明，怀孕期间激活素 A 水平的升高会引起心脏功能障碍，并支持激活素 A 可能作为 PE 引起的心脏功能障碍的潜在介质的概念。
