Department of Pediatric Cardiology and Pneumology, University Children's Hospital, Duesseldorf, Germany.
Tissue Eng Part A. 2012 Jan;18(1-2):147-56. doi: 10.1089/ten.TEA.2011.0029. Epub 2011 Oct 3.
Infective endocarditis (IE) remains a serious complication after heart valve replacement. Autologous valves constructed by matrix-based tissue engineering are under investigation to increase biocompatibility. The impact of the underlying matrix on the risk to develop IE is not known. The IE is characterized by bacterial adhesion and subsequent interactions of disseminating bacteria with endothelial cells (ECs) and monocytes, evoking endothelial proinflammatory and procoagulant activity, leading to heart valve destruction. In the current study, we, therefore, have seeded human ECs on a fibrin versus collagen gel matrix and, at confluence, infected them with Staphylococcus aureus, Streptococcus sanguis, and Staphylococcus epidermidis. Especially Sta. aureus infected ECs grown on fibrin (4.2% of the inoculum) and collagen (3.7%) matrices, more than on ECs grown on noncoated plates (1.2%; p<0.01). This was associated with higher monocyte adhesion (61%; p<0.01 on fibrin and 43%; p<0.05 on collagen) versus control cultures (30%), even at comparable EC surface expression of intercellular adhesion molecule-1 and vascular adhesion molecule-1. The collagen matrix attenuated the Sta. aureus-induced monocyte chemoattractant protein 1 expression 2.0-fold, compared with the noncoated control ECs. This reduction coincided with a 4.2-5.0-fold reduction of the procoagulant activity, triggered in ECs grown on noncoated wells, as a consequence of tissue factor (TF) expression by ECs, further stimulated by EC-bound monocytes. Overall, moderate responses were seen on infection with Str. sanguis and Sta. epidermidis for both gel matrices. Thus, even when fibrin and collagen gel matrices equally increase bacterial adhesion, and subsequent monocyte adhesion to infected ECs, these matrices modulate EC responses to these stimuli, thus resulting in attenuated cytokine production and attenuated adherent monocyte-dependent TF production by the ECs. Further investigations will need to confirm whether also in vivo, EC-matrix interactions can attenuate EC responses to bacteria and inflammatory cells to reduce IE at infected endovascular sites.
感染性心内膜炎（IE）仍然是心脏瓣膜置换术后的严重并发症。基于基质的组织工程构建的自体瓣膜正在研究中，以提高生物相容性。基底基质对 IE 风险的影响尚不清楚。IE 的特征是细菌黏附，随后扩散细菌与内皮细胞（ECs）和单核细胞相互作用，引发内皮细胞的促炎和促凝活性，导致心瓣膜破坏。在本研究中，我们因此将人 EC 接种在纤维蛋白与胶原蛋白凝胶基质上，在汇合时用金黄色葡萄球菌、链球菌和表皮葡萄球菌感染它们。特别是在纤维蛋白（4.2%的接种物）和胶原蛋白（3.7%）基质上生长的 Sta. aureus 感染的 EC 比在非涂层板上生长的 EC（1.2%；p<0.01）更多。这与更高的单核细胞黏附（61%；在纤维蛋白上 p<0.01，在胶原蛋白上 p<0.05）有关与对照培养物（30%）相比，即使 EC 表面细胞间黏附分子-1 和血管黏附分子-1 的表达相当。与非涂层对照 EC 相比，胶原蛋白基质使 Sta. aureus 诱导的单核细胞趋化蛋白 1 表达降低 2.0 倍。这种减少与组织因子（TF）表达的 EC 引起的促凝活性降低 4.2-5.0 倍有关，进一步受到 EC 结合的单核细胞的刺激。总体而言，两种凝胶基质对链球菌和表皮葡萄球菌的感染均表现出适度的反应。因此，即使纤维蛋白和胶原蛋白凝胶基质均增加细菌黏附，随后感染的 EC 上的单核细胞黏附，这些基质也调节 EC 对这些刺激的反应，从而导致细胞因子产生减少和 EC 产生的依赖黏附单核细胞的 TF 减少。进一步的研究将需要证实，即使在体内，EC-基质相互作用也可以减弱 EC 对细菌和炎症细胞的反应，从而减少感染血管内部位的 IE。
