Wang Guanglei, Lu Wenhui, Shen Wei-Bin, Karbowski Mariusz, Kaushal Sunjay, Yang Peixin
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
JACC Basic Transl Sci. 2024 Feb 14;9(3):303-318. doi: 10.1016/j.jacbts.2023.11.008. eCollection 2024 Mar.
Most congenital heart defect (CHD) cases are attributed to nongenetic factors; however, the mechanisms underlying nongenetic factor-induced CHDs are elusive. Maternal diabetes is one of the nongenetic factors, and this study aimed to determine whether impaired mitochondrial fusion contributes to maternal diabetes-induced CHDs and if mitochondrial fusion activators, teriflunomide and echinacoside, could reduce CHD incidence in diabetic pregnancy. We demonstrated maternal diabetes-activated FoxO3a increases miR-140 and miR-195, which in turn represses Mfn1 and Mfn2, leading to mitochondrial fusion defects and CHDs. Two mitochondrial fusion activators are effective in preventing CHDs in diabetic pregnancy.
大多数先天性心脏病（CHD）病例归因于非遗传因素；然而，非遗传因素诱发CHD的潜在机制尚不清楚。母体糖尿病是其中一种非遗传因素，本研究旨在确定线粒体融合受损是否会导致母体糖尿病诱发CHD，以及线粒体融合激活剂来氟米特和紫锥菊甙是否能降低糖尿病妊娠中CHD的发病率。我们证明，母体糖尿病激活的FoxO3a会增加miR-140和miR-195，进而抑制Mfn1和Mfn2，导致线粒体融合缺陷和CHD。两种线粒体融合激活剂可有效预防糖尿病妊娠中的CHD。
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