リゾホスファチジン酸がCOVID-19における血管損傷を防ぐことを世界で初めて実証

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2025-07-25  福井大学

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福井大学などの研究グループは、新型コロナウイルス感染症(COVID-19)による血管損傷に対し、脂質メディエーター「リゾホスファチジン酸(LPA)」が血管を保護する効果を持つことを世界で初めて実証しました。独自の3次元血管培養モデルと動物実験により、LPAが炎症性サイトカインの抑制や血管内皮細胞間の接着維持を通じて、血管構造を保つ仕組みを明らかにしました。従来の抗ウイルス・抗炎症薬とは異なるアプローチで、重症化やLong COVIDの予防への応用が期待されます。

リゾホスファチジン酸がCOVID-19における血管損傷を防ぐことを世界で初めて実証
図1. 3次元血管培養システムにおけるSARS-CoV-2感染とLPA保護効果(CD31陽性の管腔構造を示す蛍光顕微鏡画像)

<関連情報>

リゾホスファチジン酸による血管保護作用がSARS-CoV-2感染における血管損傷を抑制するVasoprotective effects of lysophosphatidic acid inhibit vascular injury caused by SARS-CoV-2 infection

Fumitaka Muramatsu,Naoi Hosoe,Tatsuya Suzuki,Teppei Shimamura,Yumiko Hayashi,Kazuhiro Takara,Lamri Lynda,Anna Shimizu,Weizhen Jia,Yoshimi Noda,Nobuyuki Takakura,Toru Okamoto & Hiroyasu Kidoya
Scientific Reports  Published:25 July 2025
DOI:https://doi.org/10.1038/s41598-025-06569-7

Abstract

Vasculitis and vascular injury are induced in coronavirus disease 2019 (COVID-19) patients, suggesting an association between multi-organ failure and sequelae. Vascular endothelial dysfunction induced by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) disrupts vascular barrier function, activates coagulation pathways, and induces extravasation of inflammatory cells. In addition to employing standard anti-inflammatory and antiviral agents, using treatments that stabilize and protect blood vessels following SARS-CoV-2 infection is a potentially effective strategy to relieve COVID-19 severity. Here, we focused on the vasoprotective effects of lysophosphatidic acid (LPA), a lipid mediator with diverse activities, and investigated whether it could be a novel therapeutic for COVID-19. Three-dimensional cultures of various human vascular endothelial cells that form luminal structures showed increased expression of LPA4 and entry receptors for SARS-CoV-2 infection, mimicking blood vessels in vivo. Validation using this culture system showed that LPA attenuated SARS-CoV-2 infection-induced vascular destruction and the activation of inflammatory signaling. In experiments with infected animals, LPA administration protected blood vessels and suppressed inflammation and vascular damage in lung tissue. The activation of LPA signaling in vascular endothelial cells may be an effective therapeutic approach for mitigating vascular injury in COVID-19.

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