ArticleCirculation research2023
PROX1 Inhibits PDGF-B Expression to Prevent Myxomatous Degeneration of Heart Valves.
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Article in Circulation research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 16 citations in OpenAlex.
- Valvular Leaflets Are Not Innocent Bystanders: Divergent Fibrotic Remodeling Accompanies Functional Mitral and Tricuspid Regurgitation.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Active endothelial and neural regulation of valve biology, health, and disease.Frontiers in cardiovascular medicine · 2026Review
- The role of the cardiac lymphatic system in heart failure "reverse remodeling": from developmental signals to druggable targets.Frontiers in immunology · 2026Review
- Normal cardiac lymphatics and their mimics.American journal of physiology. Heart and circulatory physiology · 2026Article
- Downregulation of serum Foxc2 in dilated cardiomyopathy: association with disease severity and cardiac function.Future science OA · 2025Article
- Spatiotemporal gene expression and cellular dynamics of the developing human heart.Nature genetics · 2025Article
- Site-1 protease-mediated cholesterol metabolism is essential for lymphatic development in mice.JCI insight · 2025Article
- Reversion of aortic valve cells calcification by activation of Notch signalling via histone acetylation induction.Signal transduction and targeted therapy · 2025Article
- Hemodynamic forces prevent myxomatous valve disease in mice through KLF2/4 signaling.The Journal of clinical investigation · 2025Article
- Aortic Regurgitation: An Updated Review of Etiologies, Diagnostic Strategies, and Clinical Management.Reviews in cardiovascular medicine · 2025Review
- Construction of a prognostic risk model for clear cell renal cell carcinomas based on centrosome amplification-related genes.Molecular genetics and genomics : MGG · 2025Article
- Profibrotic VEGFR3-Dependent Lymphatic Vessel Growth in Autoimmune Valvular Carditis.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Epicardial deletion of Sox9 leads to myxomatous valve degeneration and identifies Cd109 as a novel gene associated with valve development.Journal of molecular and cellular cardiology · 2024Article
- Integrated Pathogenesis of Vascular and Cardiac Valve Disease.Circulation research · 2023Article
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Authors and funding
26 authors at 8 institutions in 4 countries.
Yen-Chun HoCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK (Y.-C.H., X.G., R.V., K.S., Z.J.A.-N., J.K., R.S., L.C., B.C., L.X., F.L., L.E.O., J.A., R.S.S.).ORCID 0000-0001-9147-2502
Xin Geng *Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK (Y.-C.H., X.G., R.V., K.S., Z.J.A.-N., J.K., R.S., L.C., B.C., L.X., F.L., L.E.O., J.A., R.S.S.).
Anna O'Donnell *Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH (A.O., K.E.Y.).ORCID 0000-0003-4880-8394
Jaime IbarrolaMolecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (J.I.).
Amaya Fernandez-CelisCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), Pamplona, Spain (J.I., A.F.-C., N.L.-A., R.S.S.).
Rohan VarshneyCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK (Y.-C.H., X.G., R.V., K.S., Z.J.A.-N., J.K., R.S., L.C., B.C., L.X., F.L., L.E.O., J.A., R.S.S.).ORCID 0000-0002-8580-3675
Kumar SubramaniCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK (Y.-C.H., X.G., R.V., K.S., Z.J.A.-N., J.K., R.S., L.C., B.C., L.X., F.L., L.E.O., J.A., R.S.S.).ORCID 0000-0002-8478-3625
Zheila J Azartash-NaminCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK (Y.-C.H., X.G., R.V., K.S., Z.J.A.-N., J.K., R.S., L.C., B.C., L.X., F.L., L.E.O., J.A., R.S.S.).
Jang KimCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK (Y.-C.H., X.G., R.V., K.S., Z.J.A.-N., J.K., R.S., L.C., B.C., L.X., F.L., L.E.O., J.A., R.S.S.).
Robert SilasiCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK (Y.-C.H., X.G., R.V., K.S., Z.J.A.-N., J.K., R.S., L.C., B.C., L.X., F.L., L.E.O., J.A., R.S.S.).ORCID 0000-0001-9590-6160
Jill Wylie-SearsVascular Biology Program, Boston Children's Hospital, Boston, MA (J.W.-S., Z.A., H.C., J.B.).ORCID 0000-0003-3305-8578
Zahra AlvandiVascular Biology Program, Boston Children's Hospital, Boston, MA (J.W.-S., Z.A., H.C., J.B.).ORCID 0000-0003-0097-4713
Lijuan ChenCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK (Y.-C.H., X.G., R.V., K.S., Z.J.A.-N., J.K., R.S., L.C., B.C., L.X., F.L., L.E.O., J.A., R.S.S.).
Boksik ChaCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK (Y.-C.H., X.G., R.V., K.S., Z.J.A.-N., J.K., R.S., L.C., B.C., L.X., F.L., L.E.O., J.A., R.S.S.).ORCID 0000-0002-9686-879X
Hong ChenVascular Biology Program, Boston Children's Hospital, Boston, MA (J.W.-S., Z.A., H.C., J.B.).ORCID 0000-0002-1906-6611
Lijun XiaCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK (Y.-C.H., X.G., R.V., K.S., Z.J.A.-N., J.K., R.S., L.C., B.C., L.X., F.L., L.E.O., J.A., R.S.S.).ORCID 0000-0002-9586-7971
Bin ZhouDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY (B.Z.).ORCID 0000-0003-0832-4002
Florea LupuCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK (Y.-C.H., X.G., R.V., K.S., Z.J.A.-N., J.K., R.S., L.C., B.C., L.X., F.L., L.E.O., J.A., R.S.S.).
Harold M BurkhartOklahoma Children's Hospital, University of Oklahoma Health Heart Center, Oklahoma City, OK (H.M.B.).ORCID 0000-0002-2766-0418
Elena AikawaDepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (E.A.).ORCID 0000-0001-7835-2135
Lorin E OlsonCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK (Y.-C.H., X.G., R.V., K.S., Z.J.A.-N., J.K., R.S., L.C., B.C., L.X., F.L., L.E.O., J.A., R.S.S.).ORCID 0000-0003-2168-7836
Jasimuddin AhamedCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK (Y.-C.H., X.G., R.V., K.S., Z.J.A.-N., J.K., R.S., L.C., B.C., L.X., F.L., L.E.O., J.A., R.S.S.).ORCID 0000-0001-6455-0296
Natalia López-AndrésCardiovascular Translational Research, Navarrabiomed (Miguel Servet Foundation), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), Pamplona, Spain (J.I., A.F.-C., N.L.-A., R.S.S.).ORCID 0000-0003-3728-2606
Joyce BischoffVascular Biology Program, Boston Children's Hospital, Boston, MA (J.W.-S., Z.A., H.C., J.B.).ORCID 0000-0002-6367-1974
Katherine E YutzeyDivision of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH (A.O., K.E.Y.).ORCID 0000-0002-1444-7124
R Sathish SrinivasanCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK (Y.-C.H., X.G., R.V., K.S., Z.J.A.-N., J.K., R.S., L.C., B.C., L.X., F.L., L.E.O., J.A., R.S.S.).ORCID 0000-0002-4465-3340
Oklahoma Medical Research Foundation · USBoston Children's Hospital · USCincinnati Children's Hospital Medical Center · USNavarrabiomed · ESAlbert Einstein College of Medicine · USBrigham and Women's Hospital · USChildren's Hospital of Oklahoma · USTufts Medical Center · US
Funding
Viral sensor IFIH1 promotes SLE through an altered interferon programP20GM139763 · NIGMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI Kenneth M Humphries · 2021 to 2026
$20.3MMolecular Mechanisms Controlling Lymphatic Vascular Function in Health and DiseaseR01HL133216 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI CHEN, HONG, DIXON, JAMES BRANDON · 2016 to 2025
$6.7MImproving Mitral Compensation In Ischemic RegurgitationR01HL141917 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI AIKAWA, ELENA, BISCHOFF, JOYCE E. · 2018 to 2021
$5.6MMolecular and Cellular Mechanisms in Coronary Artery Development and AnomaliesR01HL133120 · NHLBI · UNIVERSITY OF CHICAGO · PI BIN ZHOU · 2016 to 2026
$4.6MDefining the Mechanisms of Lymphatic Vascular Growth and FunctionR01HL131652 · NHLBI · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI SRINIVASAN, RAJANARAYANAN S · 2016 to 2025
$3.9MThe role of signaling adaptor protein epsin in atherosclerosisR01HL156362 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI CHEN, HONG, SHI, JINJUN · 2021 to 2024
$3.1MThe Role of Adaptor Protein Disabled-2 in Maintaining Endothelial Cell Function in AtherosclerosisR01HL162367 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI CHEN, HONG, SHI, JINJUN · 2022 to 2025
$3.0MMolecular Mechanisms Governing Vascular Cell Function and Phenotype in Health and DiseaseR01HL158097 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI CHEN, HONG, CHEN, YABING · 2021 to 2024
$3.0MThe Role of TGF-beta Activation and Signaling in Aortic Stenosis ProgressionR01HL148123 · NHLBI · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI Jasimuddin Ahamed · 2020 to 2026
$2.9MRole of PXR in drug-elicited cardiovascular diseaseR01HL167206 · NHLBI · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI Hong Chen, Changcheng Zhou · 2023 to 2026
$2.8MMacrophage-derived microcalcificaitonsR01HL136431 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI AIKAWA, ELENA · 2017 to 2020
$2.7MCardiovascular Risk of Antiretroviral Therapy Drugs in HIVR01HL167656 · NHLBI · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI Jasimuddin Ahamed · 2023 to 2026
$2.7MBLRD VA I01 BX004426NHLBI NIH HHS R01 HL131652NHLBI NIH HHS R01 HL133120NHLBI NIH HHS R01 HL133216NHLBI NIH HHS R01 HL136431NHLBI NIH HHS R01 HL141917NHLBI NIH HHS R01 HL148123NHLBI NIH HHS R01 HL156270NHLBI NIH HHS R01 HL156362NHLBI NIH HHS R01 HL157347NHLBI NIH HHS R01 HL158097NHLBI NIH HHS R01 HL159515NHLBI NIH HHS R01 HL162367NHLBI NIH HHS R01 HL163095NHLBI NIH HHS R01 HL167206NHLBI NIH HHS R01 HL167656NIAMS NIH HHS R01 AR073828NIGMS NIH HHS P20 GM139763
Abstract
backgroundCardiac valve disease is observed in 2.5% of the general population and 10% of the elderly people. Effective pharmacological treatments are currently not available, and patients with severe cardiac valve disease require surgery. PROX1 (prospero-related homeobox transcription factor 1) and FOXC2 (Forkhead box C2 transcription factor) are transcription factors that are required for the development of lymphatic and venous valves. We found that PROX1 and FOXC2 are expressed in a subset of valvular endothelial cells (VECs) that are located on the downstream (fibrosa) side of cardiac valves. Whether PROX1 and FOXC2 regulate cardiac valve development and disease is not known.
methodsWe used histology, electron microscopy, and echocardiography to investigate the structure and functioning of heart valves from
resultsHistological analysis revealed that the aortic and mitral valves of
conclusionsPROX1 antagonizes PDGF-B signaling partially via FOXC2 to maintain the extracellular matrix composition and prevent myxomatous degeneration of cardiac valves.
Indexed as
Heart Valve DiseasesMitral Valve ProlapseAnimalsEndothelial CellsHumansMiceMitral ValveProspero-Related Homeobox 1 ProteinProto-Oncogene Proteins c-sisTranscription FactorsProspero-Related Homeobox 1 ProteinProto-Oncogene Proteins c-sisTranscription Factorsaortic valveendothelial cellsextracellular matrixmitral valveprolapse
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