Extracellular matrix and cyclic stretch alter fetal cardiomyocyte proliferation and maturation in a rodent model of heart hypoplasia.
Extracellular matrix and cyclic stretch alter fetal cardiomyocyte proliferation and maturation in a rodent model of heart hypoplasia.
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DOI：
10.3389/fcvm.2022.993310
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发表时间：
2022
影响因子：
3.6
通讯作者：
Black III, Lauren D.
中科院分区：
文献类型：
--
作者：
Watson, Matthew C.;Williams, Corin;Wang, Raymond M.;Perreault, Luke R.;Sullivan, Kelly E.;Stoppel, Whitney L.;Black III, Lauren D.
出生缺陷，特别是影响心脏发育的出生缺陷，是婴幼儿发病和死亡的主要原因。出生时患有心脏发育不全（心脏发育不全）疾病的婴儿往往预后不良。目前尚不清楚发育不良心脏的心肌细胞是否保留恢复生长的潜力，尽管这一知识将有利于开发心脏发育不良疾病的治疗方法。本研究的目的是确定发育不良心脏的心肌细胞的增殖和成熟潜力，以及这些行为是否受到细胞外基质（ECM）和周期性机械拉伸的生化信号的影响。通过母体暴露于除草醚，在大鼠胎儿中诱导先天性腹股沟疝（CDH）相关的心脏发育不全。从胚胎第21天的除草醚处理的胎儿CDH阳性（CDH+）和胎儿在妊娠期间没有除草醚管理分离心脏。与健康心脏相比，CDH+心脏较小，心肌增殖减少，沿着成熟度降低。在培养中，CDH+心肌细胞保持不成熟，并表现出增加的增殖能力相比，他们的健康同行。在来源于CDH+心脏的ECM上培养导致CDH+和健康心肌细胞的增殖显著减少。将外源性除草醚给予健康心肌细胞，以检查除草醚是否对心肌细胞的增殖能力具有异常影响，但未观察到增殖的显著变化。当受到拉伸时，CDH+心肌细胞的肌节延长，而健康的心肌细胞的肌节不受影响。总之，我们的研究结果表明，改变环境的线索，如ECM和拉伸可能是心脏发育不全的病理进展的重要因素。
Birth defects, particularly those that affect development of the heart, are a leading cause of morbidity and mortality in infants and young children. Babies born with heart hypoplasia (heart hypoplasia) disorders often have a poor prognosis. It remains unclear whether cardiomyocytes from hypoplastic hearts retain the potential to recover growth, although this knowledge would be beneficial for developing therapies for heart hypoplasia disorders. The objective of this study was to determine the proliferation and maturation potential of cardiomyocytes from hypoplastic hearts and whether these behaviors are influenced by biochemical signaling from the extracellular matrix (ECM) and cyclic mechanical stretch. Congenital diaphragmatic hernia (CDH)-associated heart hypoplasia was induced in rat fetuses by maternal exposure to nitrofen. Hearts were isolated from embryonic day 21 nitrofen-treated fetuses positive for CDH (CDH+) and from fetuses without nitrofen administration during gestation. CDH+ hearts were smaller and had decreased myocardial proliferation, along with evidence of decreased maturity compared to healthy hearts. In culture, CDH+ cardiomyocytes remained immature and demonstrated increased proliferative capacity compared to their healthy counterparts. Culture on ECM derived from CDH+ hearts led to a significant reduction in proliferation for both CDH+ and healthy cardiomyocytes. Healthy cardiomyocytes were dosed with exogenous nitrofen to examine whether nitrofen may have an aberrant effect on the proliferative ability of cardiomyocyte, yet no significant change in proliferation was observed. When subjected to stretch, CDH+ cardiomyocytes underwent lengthening of sarcomeres while healthy cardiomyocyte sarcomeres were unaffected. Taken together, our results suggest that alterations to environmental cues such as ECM and stretch may be important factors in the pathological progression of heart hypoplasia.
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影响因子：
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作者：
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通讯作者：
Kuehn, Bernhard
影响因子：
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作者：
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通讯作者：
Srivastava, Deepak
影响因子：
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作者：
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