Fibroblasts not only play key roles under physiological and pathological conditions in various tissues and organs including the heart but also are indispensable for fabricating bioengineered cardiac tissues and their functions through cell–cell interactions. Because tissue functions and cells surarounding fibroblasts in vivo are different among tissues, the properties of fibroblasts might be different according to their tissue origin. Understanding the molecular mechanisms of fibroblasts may lead to fabrication of bioengineered tissues close to biological tissues. In this study, we found a unique less angiogenic property of human cardiac fibroblasts in vitro compared with human dermal fibroblasts and identified the responsible gene. Cardiac fibroblasts inhibited vascular network formation in co-cultures with various types of vascular endothelial cells. Using microarray analysis and short interfering RNA (siRNA) screening experiments, we identified Ly6/Plaur domain-containing 1 (LYPD1) as responsible for the lack of endothelial cell network formation mediated by cardiac fibroblasts. Inhibition of the LYPD1 gene by siRNA attenuated the anti-angiogenic properties of cardiac fibroblasts, whereas the functional defect was rescued by addition of recombinant LYPD1. These findings suggest that cardiac fibroblasts possess anti-angiogenic properties mediated by LYPD1 and that inhibition of LYPD1 might contribute to the fabrication of vascularized functional bioengineered tissues.

成纤维细胞不仅在生理和病理条件下在包括心脏在内的各种组织和器官中起关键作用，而且对于制造生物工程化的心脏组织及其通过细胞间相互作用产生的功能也是必不可少的。由于体内组织的功能和围绕成纤维细胞的细胞在组织之间是不同的，因此成纤维细胞的特性可能会根据其组织来源而有所不同。了解成纤维细胞的分子机制可能导致靠近生物组织的生物工程组织的制造。在这项研究中，我们发现人心脏成纤维细胞在体外具有独特的较少血管生成特性与人类皮肤成纤维细胞进行比较，并鉴定出负责任的基因。在与各种类型的血管内皮细胞共培养时，心脏成纤维细胞抑制了血管网络的形成。使用微阵列分析和短干扰RNA（siRNA）筛选实验，我们确定了Ly6 / Plaur域包含1（LYPD1）是由心脏成纤维细胞介导的缺乏内皮细胞网络形成的原因。siRNA抑制LYPD1基因减弱了心脏成纤维细胞的抗血管生成特性，而通过添加重组LYPD1可以挽救功能缺陷。这些发现表明，心脏成纤维细胞具有由LYPD1介导的抗血管生成特性，并且对LYPD1的抑制可能有助于血管化功能性生物工程组织的制造。