Hypoxia Stimulates Synthesis of Neutrophil Gelatinase-Associated Lipocalin in Aortic Valve Disease

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dc.citation.articleNumber156
dc.citation.journalTitleFrontiers in Cardiovascular Medicine
dc.citation.volumeNumber6
dc.contributor.authorSwaminathan, Ganesh
dc.contributor.authorKrishnamurthy, Varun K.
dc.contributor.authorSridhar, Swetha
dc.contributor.authorRobson, Denise C.
dc.contributor.authorNing, Yao
dc.contributor.authorGrande-Allen, K. Jane
dc.date.accessioned2021-10-06T14:15:46Z
dc.date.available2021-10-06T14:15:46Z
dc.date.issued2019
dc.description.abstractObjective: Aortic valve disease is commonly found in the elderly population. It is characterized by dysregulated extracellular matrix remodeling followed by extensive microcalcification of the aortic valve and activation of valve interstitial cells. The mechanism behind these events are largely unknown. Studies have reported expression of hypoxia inducible factor-1 alpha (HIF1α) in calcific nodules in aortic valve disease, therefore we investigated the effect of hypoxia on extracellular matrix remodeling in aged aortic valves.Approach and Results: Western blotting revealed elevated expression of HIF1α and the complex of matrix metalloprotease 9 (MMP9) and neutrophil gelatinase-associated lipocalin (NGAL) in aged porcine aortic valves cultured under hypoxic conditions. Consistently, immunofluorescence staining showed co-expression of MMP9 and NGAL in the fibrosa layer of these porcine hypoxic aortic valves. Gelatinase zymography demonstrated that the activity of MMP9-NGAL complex was significantly increased in aortic valves in 13% O2 compared to 20% O2. Importantly, the presence of ectopic elastic fibers in the fibrosa of hypoxic aortic valves, also detected in human diseased aortic valves, suggests altered elastin homeostasis due to hypoxia.Conclusion: This study demonstrates that hypoxia stimulates pathological extracellular matrix remodeling via expression of NGAL and MMP9 by valve interstitial cells.
dc.identifier.citationSwaminathan, Ganesh, Krishnamurthy, Varun K., Sridhar, Swetha, et al.. "Hypoxia Stimulates Synthesis of Neutrophil Gelatinase-Associated Lipocalin in Aortic Valve Disease." <i>Frontiers in Cardiovascular Medicine,</i> 6, (2019) Frontiers: https://doi.org/10.3389/fcvm.2019.00156.
dc.identifier.digitalfcvm-06-00156
dc.identifier.doihttps://doi.org/10.3389/fcvm.2019.00156
dc.identifier.urihttps://hdl.handle.net/1911/111482
dc.language.isoeng
dc.publisherFrontiers
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleHypoxia Stimulates Synthesis of Neutrophil Gelatinase-Associated Lipocalin in Aortic Valve Disease
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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