Angiogenesis is regulated by a balance between promoting and inhibitory mechanisms. Although angiogenesis-promoting mechanisms have been well studied in ischemic heart diseases, angiogenesis-inhibitory mechanisms have not. Recently, we identified LYPD-1 as a novel anti-angiogenic factor derived from human heart-derived fibroblasts, which suppresses endothelial cell network formation in co-culture. However, it remains unclear whether the low angiogenicity of heart-derived fibroblasts with high expression of LYPD-1 is also observed in other mammalian species, and the properties of LYPD-1 under normal and pathological conditions remain elusive. Fibroblasts isolated from neonatal and adult rat heart also express LYPD-1 and inhibit endothelial network formation in co-culture. Moreover, immunohistochemical analysis revealed that LYPD-1 was predominantly observed in the interstitial tissues of rat heart and LYPD1 expression levels were identical from late developmental period to adult. Conversely, LYPD-1 mRNA expression was significantly downregulated temporally in myocardial infarction model rats, suggesting that angiogenesis-inhibitory mechanisms might not be sufficiently suppressed to promote angiogenesis in ischemic heart diseases. These findings suggest that heart has relatively low angiogenicity compared with other organs via the high expression of LYPD-1 by fibroblasts. Moreover, understanding the regulatory mechanisms of LYPD-1-mediated inhibition of angiogenesis might lead a novel angiogenic therapy for ischemic heart diseases and contribute to development of bioengineered cardiac tissue.

血管生成受促进和抑制机制之间的平衡调节。尽管在缺血性心脏病中已经很好地研究了促进血管生成的机制，但尚未对抑制血管生成的机制进行研究。最近，我们将LYPD-1鉴定为源自人心脏成纤维细胞的新型抗血管生成因子，它可抑制共培养中的内皮细胞网络形成。然而，尚不清楚在其他哺乳动物物种中是否还观察到了具有高表达LYPD-1的心脏成纤维细胞的低血管生成性，在正常和病理条件下LYPD-1的特性仍然难以捉摸。从新生和成年大鼠心脏分离的成纤维细胞还表达LYPD-1，并在共培养中抑制内皮网络的形成。此外，免疫组织化学分析显示，在大鼠心脏的间质组织中主要观察到LYPD-1，从发育后期到成年，LYPD1的表达水平相同。相反，在心肌梗塞模型大鼠中，LYPD-1 mRNA的表达在时间上显着下调，这表明在缺血性心脏病中可能未充分抑制血管生成抑制机制以促进血管生成。这些发现表明，通过成纤维细胞高表达LYPD-1，与其他器官相比，心脏具有较低的血管生成性。此外，了解LYPD-1介导的血管生成抑制作用的调控机制可能会导致针对缺血性心脏病的新型血管生成疗法，并有助于生物工程心脏组织的发展。