Metabolic regulation of collagen gel contraction by porcine aortic valvular interstitial cells
Metabolic regulation of collagen gel contraction by porcine aortic valvular interstitial cells
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DOI：
10.1098/rsif.2014.0852
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发表时间：
2014-12
影响因子：
3.9
通讯作者：
Kamel Pi;Q. X.;K. J. Grande-Allen;Peter I. Kamel;X. Qu;Andrew M. Geiszler;Deepak Nagrath;R. Harmancey;H. Taegtmeyer
中科院分区：
文献类型：
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作者：
Kamel Pi;Q. X.;K. J. Grande-Allen;Peter I. Kamel;X. Qu;Andrew M. Geiszler;Deepak Nagrath;R. Harmancey;H. Taegtmeyer
尽管钙化性主动脉瓣疾病在代谢综合征中的发病率很高，但关于心脏瓣膜基本代谢的信息却很少。细胞代谢是化学和机械刺激的第一反应者，但尚不清楚瓣膜组织工程中采用的此类信号如何影响瓣膜间质细胞（维克）生物学和瓣膜疾病发病机制。在这项研究中，将猪主动脉VIC接种到三维胶原凝胶中，并分析凝胶收缩、乳酸产生和葡萄糖消耗对代谢底物（包括葡萄糖、半乳糖、丙酮酸盐和谷氨酰胺）操作的响应。还在二维培养中评估细胞活力。我们发现，凝胶收缩是敏感的代谢操纵，特别是在营养耗尽的培养基。在中等葡萄糖浓度（2 g l−1）下收缩最佳，过量（4.5 g l−1）或减少葡萄糖（1 g l−1）时收缩较少。用半乳糖替代延迟收缩和减少乳酸产生。在低糖浓度下，丙酮酸消耗减少收缩。谷氨酰胺耗竭降低细胞代谢和活力。我们的研究结果表明，营养消耗和代谢底物的操纵影响VIC的活力，代谢和收缩行为。特别地，高血凝状态可减少维克与细胞外基质的相互作用和细胞外基质的重塑。这些结果开始将维克代谢和宏观行为（如细胞-基质相互作用）联系起来。
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.