Abstract Calcification is among the principal causes of biological heart valve substitute failure. Glycosaminoglcans (GAGs) are negatively charged molecules, possessing anticoagulation and anti-inflammatory activity that make them a potential solution against calcification. In the present work, the anticalcification potential of heparin was investigated under constant supersaturation conditions with respect to hydroxyapatite (Ca 5 (PO 4 ) 3 OH; HAP). Heparin concentration in the supersaturated solutions was in the range between 0.25 and 3 ppm, at pH 7.40 and 37 °C. Heparin showed inhibitory activity, which was attributed to adsorption at the active crystal growth centres. Heparin concentration as low as ca. 50 μM, reduced the rate of HAP crystal growth by more than 80%, while further increase (up to 200 μM) failed to completely inhibit the process beyond 90%. Heparin uptake studies at equilibrium conditions and analysis of the kinetics data in the presence of heparin, strongly suggest that the inhibition is due to the adsorption of heparin onto the HAP crystals, which resulted in the poisoning of the active growth sites.

中文翻译：

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使用恒定组成的体外模型研究肝素对羟基磷灰石种子的抗钙化潜力

摘要 钙化是生物心脏瓣膜替代失败的主要原因之一。糖胺聚糖 (GAG) 是带负电荷的分子，具有抗凝和抗炎活性，使其成为对抗钙化的潜在解决方案。在目前的工作中，肝素在恒定过饱和条件下对羟基磷灰石（Ca 5 (PO 4 ) 3 OH；HAP）的抗钙化潜力进行了研究。在 pH 7.40 和 37 °C 下，过饱和溶液中的肝素浓度范围在 0.25 到 3 ppm 之间。肝素显示出抑制活性，这归因于活性晶体生长中心的吸附。肝素浓度低至约。50 μM，降低HAP晶体生长速度80%以上，而进一步增加（高达 200 μM）未能完全抑制超过 90% 的过程。平衡条件下的肝素摄取研究和肝素存在下的动力学数据分析强烈表明抑制作用是由于肝素吸附到 HAP 晶体上，导致活性生长位点中毒。