Aasa Kristiina L, Zavan Bruno, Luna Rayana L, Wong Philip G, Ventura Nicole M, Tse M Yat, Carmeliet Peter, Adams Michael A, Pang Stephen C, Croy B Anne
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario Canada
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario Canada Department of Cell, Tissue and Developmental Biology, Federal University of Alfenas, Alfenas MG, Brazil.
Biol Reprod. 2015 Feb;92(2):44. doi: 10.1095/biolreprod.114.124677. Epub 2014 Dec 23.
In healthy human pregnancies, placental growth factor (PGF) concentrations rise in maternal plasma during early gestation, peak over Weeks 26-30, then decline. Because PGF in nongravid subjects participates in protection against and recovery from cardiac pathologies, we asked if PGF contributes to pregnancy-induced maternal cardiovascular adaptations. Cardiovascular function and structure were evaluated in virgin, pregnant, and postpartum C56BL/6-Pgf(-) (/) (-) (Pgf(-) (/) (-)) and C57BL/6-Pgf(+/+) (B6) mice using plethysmography, ultrasound, quantitative PCR, and cardiac and renal histology. Pgf(-/-) females had higher systolic blood pressure in early and late pregnancy but an extended, abnormal midpregnancy interval of depressed systolic pressure. Pgf(-/-) cardiac output was lower than gestation day (gd)-matched B6 after midpregnancy. While Pgf(-) (/) (-) left ventricular mass was greater than B6, only B6 showed the expected gestational gain in left ventricular mass. Expression of vasoactive genes in the left ventricle differed at gd8 with elevated Nos expression in Pgf(-) (/) (-) but not at gd14. By gd16, Pgf(-) (/) (-) kidneys were hypertrophic and had glomerular pathology. This study documents for the first time that PGF is associated with the systemic maternal cardiovascular adaptations to pregnancy.
在健康的人类妊娠中，妊娠早期母血中胎盘生长因子（PGF）浓度升高，在第26 - 30周达到峰值，然后下降。由于非妊娠个体中的PGF参与预防心脏疾病并促进心脏疾病恢复，我们探究PGF是否有助于孕期母体心血管系统的适应性变化。使用体积描记法、超声、定量PCR以及心脏和肾脏组织学方法，对未孕、妊娠和产后的C56BL/6-Pgf(- / -)（Pgf(- / -)）和C57BL/6-Pgf(+/+)（B6）小鼠的心血管功能和结构进行评估。Pgf(- / -)雌性小鼠在妊娠早期和晚期收缩压较高，但在妊娠中期出现收缩压降低的异常延长阶段。妊娠中期后，Pgf(- / -)小鼠的心输出量低于与之妊娠天数（gd）匹配的B6小鼠。虽然Pgf(- / -)小鼠的左心室质量大于B6小鼠，但只有B6小鼠的左心室质量呈现预期的孕期增加。在gd8时，左心室中血管活性基因的表达存在差异，Pgf(- / -)小鼠中Nos表达升高，但在gd14时无此差异。到gd16时，Pgf(- / -)小鼠的肾脏肥大并出现肾小球病变。本研究首次证明PGF与孕期母体全身心血管系统的适应性变化有关。
