Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA.
Int J Mol Sci. 2023 Oct 17;24(20):15249. doi: 10.3390/ijms242015249.
Hypoplastic left heart syndrome (HLHS) is a lethal congenital heart disease (CHD) affecting 8-25 per 100,000 neonates globally. Clinical interventions, primarily surgical, have improved the life expectancy of the affected subjects substantially over the years. However, the etiological basis of HLHS remains fundamentally unclear to this day. Based upon the existing paradigm of studies, HLHS exhibits a multifactorial mode of etiology mediated by a complicated course of genetic and signaling cascade. This review presents a detailed outline of the HLHS phenotype, the prenatal and postnatal risks, and the signaling and molecular mechanisms driving HLHS pathogenesis. The review discusses the potential limitations and future perspectives of studies that can be undertaken to address the existing scientific gap. Mechanistic studies to explain HLHS etiology will potentially elucidate novel druggable targets and empower the development of therapeutic regimens against HLHS in the future.
左心发育不全综合征（HLHS）是一种致命的先天性心脏病（CHD），全球每 10 万新生儿中有 8-25 例。多年来，临床干预措施，主要是手术，极大地提高了受影响患者的预期寿命。然而，HLHS 的病因基础至今仍未得到根本阐明。基于现有的研究范式，HLHS 表现出一种多因素的病因模式，由遗传和信号级联的复杂过程介导。这篇综述详细介绍了 HLHS 的表型、产前和产后风险，以及导致 HLHS 发病机制的信号和分子机制。综述讨论了为解决现有科学差距而可以开展的研究的潜在局限性和未来展望。解释 HLHS 病因的机制研究将有可能阐明新的可药物治疗靶点，并为未来针对 HLHS 的治疗方案的制定提供支持。
