2026-03-18 京都大学
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＜関連情報＞
- https://www.kyoto-u.ac.jp/ja/research-news/2026-03-18
- chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.kyoto-u.ac.jp/sites/default/files/2026-03/web_2603_Yanagisawa_j-cafb088c2cb290df00ab614af1ab0a01.pdf
- https://www.nature.com/articles/s41467-026-70139-2#citeas
血管内皮におけるC型ナトリウム利尿ペプチド/グアニル酸シクラーゼBシグナル経路は肺動脈性高血圧症を予防する Endothelial C-type natriuretic peptide/guanylyl cyclase-B signaling prevents pulmonary arterial hypertension
Hiromu Yanagisawa,Koichiro Kuwahara,Yasuaki Nakagawa,Kenji Moriuchi,Hideyuki Kinoshita,Hideaki Inazumi,Takahiko Kanamori,Toshio Nishikimi,Miku Oya,Kazuhiro Nakao,Yohei Ueda,Daisuke Nakamura,Kimihiro Shimizu,Koji Yoshie,Satona Tanaka,Daisuke Nakajima,Ichiro Sakanoue,Akihiro Yasoda,Kazuwa Nakao,Takeshi Kimura & Koh Ono
Nature Communications Published:17 March 2026
DOI:https://doi.org/10.1038/s41467-026-70139-2
Abstract
C-type natriuretic peptide (CNP) is released from endothelial cells and acts as an autocrine/paracrine mediator, regulating systemic blood pressure and vascular remodeling via guanylyl cyclase-B (GC-B) and natriuretic peptide receptor-C. We investigate the impact of vascular CNP/GC-B signaling on the development of pulmonary arterial hypertension (PAH). Mice developing pulmonary hypertension (PH) show reduced pulmonary NPPC and NPR2 expression than mice without PH. Similarly, endothelial cells (EC) from patients with idiopathic PAH exhibit lower NPPC and NPR2 expression than control EC. EC-specific CNP or GC-B conditional knockout (CNP ecKO or GC-B ecKO) mice, but not smooth muscle cell-specific GC-B conditional knockout (GC-B smcKO) mice, show more severe PH and greater expression of Edn1, Il6, Ccl2 and Tgfb1 mRNAs than their genetic controls in PAH models. CNP suppresses hypoxia-induced increases in expression of these mRNAs and restored SMAD2/3-SMAD1/5/9 balance in cultured human pulmonary arterial EC. Moreover, CNP administration prevents PH in genetic control and GC-B-smcKO mice but not in GC-B ecKO mice. CNP administration also has therapeutic effects against Sugen5416-hypoxia PAH models as well as additive benefits with established therapies. Endothelial CNP/GC-B signaling thus exerts pivotal preventative effects against development of PH, suggesting the therapeutic potential of CNP for PAH.
