自噬参与高糖介导的心血管畸形
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Autophagy is involved in high glucose-induced heart tube malformation
背景与目的
孕前或妊娠期糖尿病会对心脏产生不利影响，但是其对早期心血管系统的影响了解甚少。
方 法
我们使用小鸡早期发育的胚胎,研究高糖对心脏脉管系统形成过程的影响,特别是在心脏发育的主要早期阶段。
结 果
结果表明高糖暴露可导致3种心血管畸形：1)心室肥大，2)右位心伴心室肥大,3)心室肥大和右位心伴双侧脉管异常。接下来的实验中,我们发现这些畸形心血管可能主要源自心脏异常发育的早期中胚层细胞而，不是发育过程中心原基。
雷帕霉素为一种自噬诱导物, 可导致类似高糖介导的心血管畸形。此外,高糖暴露促进与自噬相关的蛋白LC3B的表达，且在双侧脉管系统可检测到Atg7高表达。
结 论
自噬可能参与高血糖介导的心脏脉管畸形的发育过程。
原始文献摘要
Wang G, Huang WQ, Cui SD,et al.Autophagy is involved in high glucose-induced heart tube malformation.Cell Cycle. 2015;14(5):772-83. doi: 10.1080/15384101.2014.1000170.
Background:Both pre-gestational and gestational diabetes have an adverse impact on heart development, but little is known about the influence on the early stage of heart tube formation.
Methods:Using early gastrulating chick embryos, we investigated the influence of high glucose on the process of heart tube formation, specifically during the primary heart field phase.
Results:We demonstrated that high-glucose exposure resulted in 3 types of heart tube malformation: 1) ventricular hypertrophy, 2) ventricular hypertrophy with dextrocardia and 3) ventricular hypertrophy and dextrocardia with the fusion anomaly of a bilateral primary heart tube. Next, we found that these malformation phenotypes of heart tubes might mainly originate from the migratory anomaly of gastrulating precardiac mesoderm cells rather than cell proliferation in the developmental process of bilateral primary heart field primordia. The treatment of rapamycin (RAPA), an autophagy inducer, led to a similar heart tube malformation phenotype as high glucose. Additionally, high-glucose exposure promoted the expression of the key autophagy protein LC3B in early chick tissue. Atg7 is strongly expressed in the fusion site of bilateral primary heart tubes.
Conclusions:All of these data imply that autophagy could be involved in the process of high-glucose-induced malformation of the heart tube.
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