title: Metabolic regulation of collagen gel contraction by porcine aortic valvular interstitial cells.
abstract: Despite 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.
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77005, USA.
authors.forename: Peter I
authors.initials: PI
authors.lastname: Kamel
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX 77005, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Qu
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX 77005, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Geiszler
authors.affiliation: Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX 77005, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Nagrath
authors.affiliation: Department of Internal Medicine, Division of Cardiology, The University of Texas Medical School at Houston, Houston, TX 77030, USA.
authors.forename: Romain
authors.initials: R
authors.lastname: Harmancey
authors.affiliation: Department of Internal Medicine, Division of Cardiology, The University of Texas Medical School at Houston, Houston, TX 77030, USA.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Taegtmeyer
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX 77005, USA grande@rice.edu.
authors.forename: K Jane
authors.initials: KJ
authors.lastname: Grande-Allen
mesh_terms: D000818:Animals; D001021:Aortic Valve / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival; D003094:Collagen / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D005690:Galactose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006349:Heart Valve Diseases / Q000378:metabolism* / Q000473:pathology; D019344:Lactic Acid / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism; D013552:Swine
chemical_list: D019344:Lactic Acid; D018698:Glutamic Acid; D019289:Pyruvic Acid; D003094:Collagen; D005947:Glucose; D005690:Galactose
keywords: aortic valvular interstitial cell; collagen gel; valve metabolism