Key result
Gel contraction by porcine aortic valvular interstitial cells was optimal at 2 g/L glucose, with reduced contraction at excess (4.5 g/L) or reduced (1 g/L) glucose concentrations.
Nutrient depletion and hyperglycemic conditions reduce valvular interstitial cell interaction with and remodeling of the extracellular matrix, providing insight into the pathogenesis of calcific aortic valve disease.
Glucose extremes may impair valvular interstitial cell matrix remodeling; hypothesis-generating for calcific aortic valve disease pathogenesis in humans.
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.
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Kamel et al. (2014) studied Calcific aortic valve disease. Manipulation of metabolic substrates (glucose, galactose, pyruvate, glutamine) vs. Different concentrations of substrates was evaluated on Gel contraction, lactate production, glucose consumption, and cell viability. Gel contraction by porcine aortic valvular interstitial cells was optimal at 2 g/L glucose, with reduced contraction at excess (4.5 g/L) or reduced (1 g/L) glucose concentrations.
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