Sphingosine kinase 1 is integral for elastin deficiency-induced arterial hypermuscularization.
Junichi Saito, Jui M Dave, Eunate Gallardo-Vara, Nandhini Sadagopan, Inamul Kabir, George Tellides, Robert K Riemer, Zsolt Urban, Sarah Spiegel, Timothy Hla and 1 more
Article in Nature cardiovascular research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
2 · The registry
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
5 · Who and what money
Authors and funding
11 authors.
Junichi SaitoDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, New Haven, CT, USA. jsaito@augusta.edu.ORCID http://orcid.org/0000-0002-4297-727X
Jui M DaveDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, New Haven, CT, USA.
Eunate Gallardo-VaraDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, New Haven, CT, USA.
Nandhini SadagopanDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, New Haven, CT, USA.
Inamul KabirDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-6207-1785
George TellidesDepartment of Surgery, Yale University, New Haven, CT, USA.
Robert K RiemerCongenital Division, Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Zsolt UrbanDepartment of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
Sarah SpiegelDepartment of Cellular, Molecular and Genetic Medicine, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
Daniel M GreifDepartment of Internal Medicine, Section of Cardiovascular Medicine, Yale Cardiovascular Research Center, New Haven, CT, USA. daniel.greif@yale.edu.ORCID http://orcid.org/0000-0002-9842-3751
Funding
Novel vascular smooth muscle cell progenitors in development and diseaseR35HL150766 · NHLBI · YALE UNIVERSITY · PI Daniel Greif · 2020 to 2026
$7.0M
Epigenetic-mediated Notch pathway activation promotes elastin aortopathyR01HD110059 · NICHD · YALE UNIVERSITY · PI Daniel Greif, Kathleen Ann Martin · 2023 to 2026
$2.6M
Sphingolipid signaling in age-associated vascular pathologyR01AG078602 · NIA · BOSTON CHILDREN'S HOSPITAL · PI Timothy Tun Hla · 2022 to 2026
$2.5M
Pathological arterial muscularization and the role of integrinsR01HL125815 · NHLBI · YALE UNIVERSITY · PI GREIF, DANIEL · 2015 to 2018
$1.7M
Sphingosine kinase 1 plays a key role in defective elastin-induced arterial hypermuscularizationR00HL171838 · NHLBI · AUGUSTA UNIVERSITY · PI Junichi Saito · 2025 to 2026
$498k
Sphingosine kinase 1 plays a key role in defective elastin-induced arterial hypermuscularizationK99HL171838 · NHLBI · YALE UNIVERSITY · PI SAITO, JUNICHI · 2024 to 2025
$279k
American Heart Association (American Heart Association, Inc.) 19EIA34660321American Heart Association (American Heart Association, Inc.) 23CSA1051139American Heart Association (American Heart Association, Inc.) 23POSTCHF1022933MEXT | Japan Society for the Promotion of Science (JSPS) 202260284NHLBI NIH HHS K99 HL171838NHLBI NIH HHS R00 HL171838NHLBI NIH HHS R01 HL125815NHLBI NIH HHS R35 HL150766NIA NIH HHS R01 AG078602NICHD NIH HHS R01 HD110059U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) R01HD110059U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) K99HL171838U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R00HL171838U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL125815U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R35HL150766U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG078602
6 · The paper itself
Abstract
Deficiency of elastin (ELN), the major component of elastic fibers, leads to excess smooth muscle cells (SMCs), which characterizes arterial diseases (for example, supravalvular aortic stenosis (SVAS)) as well as physiological ductus arteriosus (DA) closure. Here we demonstrate that sphingosine kinase 1 (SPHK1) is a key node in these contexts. Sphk1 is the most upregulated transcript in Eln(-/-) aortic SMCs at embryonic day 15.5 when these cells are initially hyperproliferative. The aorta of humans with SVAS also upregulates SPHK1. Reduced ELN increases levels of transcription factor early growth response 1, resulting in increased SPHK1 levels. SMC-specific Sphk1 deletion or pharmacological inhibition of SPHK1 attenuates SMC proliferation and mitigates aortic disease. Furthermore, treatment with a SPHK1 inhibitor reduces DA SMC accumulation, leading to DA patency in wild-type mice. These findings indicate that inhibiting SPHK1 may be a therapeutic strategy for SVAS and select congenital heart diseases in which patent DA maintains circulation.
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.
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