CNC-UC-Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, 3004-504 Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-504 Coimbra, Portugal; University of Coimbra, Institute for Interdisciplinary Research, PDBEB - Doctoral Programme in Experimental Biology and Biomedicine, Coimbra, Portugal.
CNC-UC-Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, 3004-504 Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-504 Coimbra, Portugal.
Biochim Biophys Acta Mol Basis Dis. 2025 Jan;1871(1):167539. doi: 10.1016/j.bbadis.2024.167539. Epub 2024 Oct 6.
Pregnancy may be a challenging period for the maternal systems and has been regarded as a stress test, as imperceptible/mild dysfunctions eventually present may be exacerbated during this period. The cardiovascular system is no exception, and several morphological and functional adaptations accompanying pregnancy have been described. However, long-term pregnancy-induced cardiac molecular alterations remain highly unexplored. The postpartum is marked by reverse remodeling of the pregnancy-induced cardiovascular adaptations, representing a possible critical period for assessing future maternal cardiovascular health. The current study explored the molecular and metabolic alterations in the cardiac tissue eight weeks after a physiological uncomplicated pregnancy. Female Sprague-Dawley rats were fed a chow diet through pregnancy, lactation, and weaning and compared to their non-pregnant counterparts. Eight weeks postpartum, increased levels of the phosphorylated form of AMPKα (Thr172) and its ratio to total AMPKα indicated possible alterations in cardiac metabolic flexibility, accompanied by increased Pparα and Hif1α transcripts levels. Additionally, postpartum hearts exhibited higher mitochondrial ATP and NADH levels without major changes in mitochondrial respiratory function. Elevated Nrf2 levels in the cardiac tissue suggested potential implications for cardiac redox balance, further supported by increased levels or activity of proteins directly regulated by Nrf2. The findings herein reported suggest that at eight weeks postpartum, molecular alterations induced by pregnancy, especially regarding redox balance, are still observed in the mothers' heart. These alterations present at late postpartum may open new avenues to understand the different risk for cardiovascular complications development after normal pregnancies.
妊娠可能是母体系统的一个挑战时期,被认为是一个应激测试,因为在此期间,即使是细微的/轻度的功能障碍也可能会加剧。心血管系统也不例外,已经描述了伴随妊娠的几种形态和功能适应性改变。然而,长期的妊娠引起的心脏分子改变仍然高度未知。产后以妊娠引起的心血管适应性的逆向重构为标志,这可能是评估未来产妇心血管健康的一个关键时期。本研究探讨了生理上无并发症妊娠 8 周后心脏组织的分子和代谢变化。雌性 Sprague-Dawley 大鼠在妊娠、哺乳期和断奶期通过喂养标准饮食,并与未怀孕的大鼠进行比较。产后 8 周,磷酸化 AMPKα(Thr172)及其与总 AMPKα的比值升高,表明心脏代谢灵活性可能发生改变,同时 Pparα 和 Hif1α 转录本水平升高。此外,产后心脏的线粒体 ATP 和 NADH 水平升高,但线粒体呼吸功能没有明显变化。心脏组织中 Nrf2 水平升高表明心脏氧化还原平衡可能存在潜在影响,这进一步得到了由 Nrf2 直接调节的蛋白质水平或活性升高的支持。本研究报告的结果表明,在产后 8 周时,妊娠引起的分子改变,特别是与氧化还原平衡有关的改变,仍在母亲的心脏中观察到。这些产后晚期出现的改变可能为理解正常妊娠后心血管并发症发展的不同风险开辟新途径。