Hypoplastic left heart syndrome (HLHS): molecular pathogenesis and emerging drug targets for cardiac repair and regeneration.
Hypoplastic left heart syndrome (HLHS): molecular pathogenesis and emerging drug targets for cardiac repair and regeneration.
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DOI：
10.1080/14728222.2021.1978069
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发表时间：
2021-08
影响因子：
5.8
通讯作者：
Gu M
中科院分区：
文献类型：
--
作者：
Bejjani AT;Wary N;Gu M
左心发育不全综合征（HLHS）是一种严重的发育缺陷，其特征是左心室发育不全沿着主动脉和瓣膜缺陷。需要多次姑息手术才能生存。新兴的研究已经确定了疾病发作的潜在机制，包括遗传和血液动力学原因。与HLHS相关的遗传变异包括正常心脏发育所必需的转录因子、染色质重塑因子、结构蛋白和信号蛋白。尽管如此，目前的治疗方法正在临床上进行测试，并在改善接受姑息手术的患者的心脏功能方面显示出有希望的结果。我们搜索了PubMed和clinicaltrials.gov来回顾大多数涉及HLHS的机制研究和临床试验。本文综述了HLHS心脏的解剖和病理。我们强调一些已确定的遗传变异的分子发病机制的HLHS。此外，我们还讨论了一些新兴的HLHS疗法及其局限性。虽然HLHS的病因在很大程度上是模糊的，姑息治疗仍然是最可行的选择的患者。有必要建立动物和干细胞模型，以了解直接导致HLHS的潜在遗传原因，并促进使用基于基因的治疗来改善心脏发育和再生。
Hypoplastic left heart syndrome (HLHS) is a severe developmental defect characterized by the underdevelopment of the left ventricle along with aortic and valvular defects. Multiple palliative surgeries are required for survival. Emerging studies have identified potential mechanisms for the disease onset, including genetic and hemodynamic causes. Genetic variants associated with HLHS include transcription factors, chromatin remodelers, structural proteins, and signaling proteins necessary for normal heart development. Nonetheless, current therapies are being tested clinically and have shown promising results at improving cardiac function in patients who have undergone palliative surgeries. We searched PubMed and clinicaltrials.gov to review most of the mechanistic research and clinical trials involving HLHS. This review discusses the anatomy and pathology of HLHS hearts. We highlight some of the identified genetic variants that underly the molecular pathogenesis of HLHS. Additionally, we discuss some of the emerging therapies and their limitations for HLHS. While HLHS etiology is largely obscure, palliative therapies remain the most viable option for the patients. It is necessary to generate animal and stem cell models to understand the underlying genetic causes directly leading to HLHS and facilitate the use of gene-based therapies to improve cardiac development and regeneration.
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影响因子：
11.8
作者：
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影响因子：
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Slaugenhaupt SA
DOI：
10.1016/j.bbrc.2016.04.036
发表时间：
2016-05-13
影响因子：
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作者：
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