线粒体融合的小分子激活剂可以预防由母体糖尿病引起的先天性心脏缺陷

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Guanglei Wang¹, Wenhui Lu¹, Wei-Bin Shen¹

¹Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.

JACC. Basic to translational science

|April 1, 2024

概括

母亲糖尿病可以通过损害线粒体融合引起先天性心脏缺陷 (CHD). 激活剂,如teriflunomide和echinacoside显示在预防糖尿病怀孕中心血管疾病方面具有前途.

科学领域:

发育生物学是发展生物学.
线粒体生物学线粒体生物学
心血管研究的心血管研究.

背景情况:

先天性心脏缺陷 (CHD) 是常见的出生缺陷,非遗传因素起着重要作用.
非遗传因素诱导CHD的确切机制在很大程度上是未知的.
孕产妇糖尿病是心血管疾病的已知风险因素,但其潜在的分子途径尚未完全阐明.

研究的目的:

为了调查是否受损的线粒体融合在孕产妇糖尿病的背景下有助于心血管疾病.
评估线粒体融合激活剂,特里弗卢诺米德和埃奇纳科西德在减轻糖尿病怀孕期间心血管疾病的潜力.

主要方法:

利用糖尿病怀孕的小鼠模型.
分析了关键调节分子 (FoxO3a,microRNAs) 和线粒体融合蛋白 (Mfn1,Mfn2) 的表达.
评估了后代中冠状动脉疾病的发病率以及特里弗卢诺米德和乙化治疗的影响.

主要成果:

母亲糖尿病导致FoxO3a的激活,从而增加了miR-140和miR-195的表达.
升高的miR-140和miR-195抑制了Mfn1和Mfn2的表达,这对线粒体融合至关重要.
这种抑制导致线粒体融合缺陷和后代中冠状动脉疾病的发病率较高.
用特里弗卢诺米德和埃希纳科赛德治疗有效地减少了糖尿病怀孕中心脏病发病率.

结论:

由FoxO3a/miR-140/miR-195通路驱动的受损线粒体融合,是孕产妇糖尿病诱导的冠状动脉疾病的关键机制.
特里弗卢诺米德和埃奇纳科西德在糖尿病复杂的怀孕中显示出预防心血管疾病的治疗潜力.

关键词:

有先天性心脏缺陷.母亲糖尿病母亲糖尿病这是一个微型RNA.线粒体融合是指线粒体的融合.米托素 1 1 线粒体素 2 2 的使用.

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