Metabolic regulation of collagen gel contraction by porcine aortic valvular interstitial cells

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dc.citation.firstpage20140852
dc.citation.issueNumber101
dc.citation.journalTitleJournal of The Royal Society Interface
dc.citation.volumeNumber11
dc.contributor.authorKamel, Peter I.
dc.contributor.authorQu, Xin
dc.contributor.authorGeiszler, Andrew M.
dc.contributor.authorNagrath, Deepak
dc.contributor.authorHarmancey, Romain
dc.contributor.authorTaegtmeyer, Heinrich
dc.contributor.authorGrande-Allen, K.Jane
dc.date.accessioned2014-11-21T21:26:58Z
dc.date.available2014-11-21T21:26:58Z
dc.date.issued2014
dc.description.abstractDespite a high incidence of calcific aortic valve disease in metabolic syndrome, there is little information about the fundamental metabolism of heart valves. Cell metabolism is a first responder to chemical and mechanical stimuli, but it is unknown how such signals employed in valve tissue engineering impact valvular interstitial cell (VIC) biology and valvular disease pathogenesis. In this study porcine aortic VICs were seeded into three-dimensional collagen gels and analysed for gel contraction, lactate production and glucose consumption in response to manipulation of metabolic substrates, including glucose, galactose, pyruvate and glutamine. Cell viability was also assessed in two-dimensional culture. We found that gel contraction was sensitive to metabolic manipulation, particularly in nutrient-depleted medium. Contraction was optimal at an intermediate glucose concentration (2 g l−1) with less contraction with excess (4.5 g l−1) or reduced glucose (1 g l−1). Substitution with galactose delayed contraction and decreased lactate production. In low sugar concentrations, pyruvate depletion reduced contraction. Glutamine depletion reduced cell metabolism and viability. Our results suggest that nutrient depletion and manipulation of metabolic substrates impacts the viability, metabolism and contractile behaviour of VICs. Particularly, hyperglycaemic conditions can reduce VIC interaction with and remodelling of the extracellular matrix. These results begin to link VIC metabolism and macroscopic behaviour such as cell–matrix interaction.
dc.identifier.citationKamel, Peter I., Qu, Xin, Geiszler, Andrew M., et al.. "Metabolic regulation of collagen gel contraction by porcine aortic valvular interstitial cells." <i>Journal of The Royal Society Interface,</i> 11, no. 101 (2014) The Royal Society: 20140852. http://dx.doi.org/10.1098/rsif.2014.0852.
dc.identifier.doihttp://dx.doi.org/10.1098/rsif.2014.0852
dc.identifier.urihttps://hdl.handle.net/1911/78488
dc.language.isoeng
dc.publisherThe Royal Society
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by The Royal Society.
dc.subject.keywordaortic valvular interstitial cell
dc.subject.keywordcollagen gel
dc.subject.keywordvalve metabolism
dc.titleMetabolic regulation of collagen gel contraction by porcine aortic valvular interstitial cells
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpost-print
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