Taube Nicole, Steiner Morgan, Ebenebe-Kasonde Obialunanma V, Kabir Raihan, Garbus-Grant Haley, Alam El Din Sarah-Marie, Illingworth Emily, Wang Nadan, Lin Brian L, Kohr Mark J
Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States.
Cardiology Division, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
Am J Physiol Heart Circ Physiol. 2025 Mar 1;328(3):H460-H471. doi: 10.1152/ajpheart.00266.2024. Epub 2025 Jan 31.
Cardiovascular disease is the leading cause of mortality in the United States. Studies suggest a role for environmental exposures in the etiology of cardiovascular disease, including exposure to arsenic through drinking water. Arsenic exposure during pregnancy has been shown to have effects on offspring, but few studies have examined impacts on maternal cardiovascular health. Although our prior work documented the detrimental effect of arsenic on the maternal heart during pregnancy, our current study examines the effect of gestational arsenic exposure on the maternal heart postpartum. Timed-pregnant wild-type (C57BL/6J) mice were exposed to 0, 100, or 1,000 µg/L sodium arsenite (NaAsO) via drinking water from until parturition. Postpartum heart structure and function was assessed via transthoracic echocardiography and gravimetric measurement. Hypertrophic markers were probed via qRT-PCR and Western blot. Isolated cardiomyocyte Ca-handling and contraction were also assessed, along with the expression of with Ca-handling and contractile proteins. Interestingly, we found that exposure to either 100 or 1,000 µg/L sodium arsenite increased postpartum heart size at vs. nonexposed postpartum controls. At the cellular level, we found altered cardiomyocyte Ca-handling and contraction, along with expression changes of key contractile proteins, including α-actin and cardiac myosin binding protein C (cMyBP-c). Together, these findings suggest that gestational arsenic exposure impacts the postpartum maternal heart, possibly inducing long-term cardiovascular changes. Furthermore, these findings highlight the importance of reducing arsenic exposure during pregnancy, and the need for more research on the impact of arsenic on maternal heart health and adverse pregnancy events. Gestational exposure to sodium arsenite at environmentally relevant doses (100 and 1,000 µg/L) increases postpartum heart size, and induces dysregulated Ca homeostasis and impaired shortening in isolated cardiomyocytes. This is the first study to demonstrate that gestational arsenic exposure impacts postpartum heart structure and function beyond the exposure period.
心血管疾病是美国的主要死因。研究表明，环境暴露在心血管疾病的病因中起作用，包括通过饮用水接触砷。孕期接触砷已被证明会对后代产生影响，但很少有研究考察其对孕产妇心血管健康的影响。尽管我们之前的研究记录了孕期砷对孕产妇心脏的有害影响，但我们目前的研究考察了孕期砷暴露对产后孕产妇心脏的影响。将定时怀孕的野生型（C57BL/6J）小鼠从[具体起始时间]至分娩期间通过饮用水暴露于0、100或1000μg/L的亚砷酸钠（NaAsO）中。通过经胸超声心动图和重量测量评估产后心脏结构和功能。通过qRT-PCR和蛋白质印迹法检测肥厚标志物。还评估了分离的心肌细胞的钙处理和收缩情况，以及钙处理和收缩蛋白的表达。有趣的是，我们发现，与未暴露的产后对照组相比，暴露于100或1000μg/L亚砷酸钠会增加产后心脏大小。在细胞水平上，我们发现心肌细胞的钙处理和收缩发生改变，同时关键收缩蛋白的表达也发生变化，包括α-肌动蛋白和心肌肌球蛋白结合蛋白C（cMyBP-c）。总之，这些发现表明孕期砷暴露会影响产后孕产妇心脏，可能导致长期心血管变化。此外，这些发现凸显了孕期减少砷暴露的重要性，以及需要更多关于砷对孕产妇心脏健康和不良妊娠事件影响的研究。孕期暴露于环境相关剂量（100和1000μg/L）的亚砷酸钠会增加产后心脏大小，并导致分离的心肌细胞钙稳态失调和缩短受损。这是第一项证明孕期砷暴露会在暴露期之外影响产后心脏结构和功能的研究。
