线粒体融合小分子激活剂可预防母体糖尿病诱发的先天性心脏缺陷

IF 8.4 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS JACC: Basic to Translational Science Pub Date : 2024-03-01 DOI:10.1016/j.jacbts.2023.11.008

Guanglei Wang PhD , Wenhui Lu PhD , Wei-Bin Shen PhD , Mariusz Karbowski PhD , Sunjay Kaushal MD, PhD , Peixin Yang PhD

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引用次数: 0

摘要

大多数先天性心脏缺陷（CHD）病例归因于非遗传因素；然而，非遗传因素诱发CHD的机制尚不明确。母体糖尿病是非遗传因素之一，本研究旨在确定线粒体融合受损是否是母体糖尿病诱发先天性心脏病的原因，以及线粒体融合激活剂特立氟脲苷和棘阿糖苷是否能降低糖尿病妊娠的先天性心脏病发病率。我们证明了母体糖尿病激活的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导致的先天性心脏病。

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Small Molecule Activators of Mitochondrial Fusion Prevent Congenital Heart Defects Induced by Maternal Diabetes

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.

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来源期刊

JACC: Basic to Translational Science CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

14.20

自引率

1.00%

发文量

161

审稿时长

16 weeks

期刊介绍： JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.