{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T01:10:15Z","timestamp":1789002615507,"version":"build-2803163510"},"reference-count":153,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T00:00:00Z","timestamp":1697500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Heart, Lung, and Blood Institute","award":["2R01HL121700-06A1"],"award-info":[{"award-number":["2R01HL121700-06A1"]}]},{"name":"National Heart, Lung, and Blood Institute","award":["20TPA35490051"],"award-info":[{"award-number":["20TPA35490051"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["2R01HL121700-06A1"],"award-info":[{"award-number":["2R01HL121700-06A1"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["20TPA35490051"],"award-info":[{"award-number":["20TPA35490051"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypoplastic left heart syndrome (HLHS) is a lethal congenital heart disease (CHD) affecting 8\u201325 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.<\/jats:p>","DOI":"10.3390\/ijms242015249","type":"journal-article","created":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T08:08:33Z","timestamp":1697530113000},"page":"15249","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Hypoplastic Left Heart Syndrome: Signaling &amp; Molecular Perspectives, and the Road Ahead"],"prefix":"10.3390","volume":"24","author":[{"given":"Sayantap","family":"Datta","sequence":"first","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7249-8492","authenticated-orcid":false,"given":"Wangjia","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikayla","family":"Skillman","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0155-2328","authenticated-orcid":false,"given":"Mingfu","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e010893","DOI":"10.1161\/JAHA.118.010893","article-title":"Changing epidemiology of hypoplastic left heart syndrome: Results of a national Swedish cohort study","volume":"8","author":"Bergman","year":"2019","journal-title":"J. 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