Heart-derived fibroblasts express LYPD-1 and negatively regulate angiogenesis in rat

Satoru Sakamoto; Katsuhisa Matsuura; Shinako Masuda; Nobuhisa Hagiwara; Tatsuya Shimizu

doi:10.1016/j.reth.2020.03.010

Heart-derived fibroblasts express LYPD-1 and negatively regulate angiogenesis in rat

Regen Ther. 2020 May 29:15:27-33. doi: 10.1016/j.reth.2020.03.010. eCollection 2020 Dec.

Authors

Satoru Sakamoto^{1

2}, Katsuhisa Matsuura^{1

2}, Shinako Masuda¹, Nobuhisa Hagiwara², Tatsuya Shimizu¹

Affiliations

¹ Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan.
² Department of Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan.

Abstract

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.

Keywords: Angiogenesis; Heart-derived fibroblast; LYPD1.