Omega-3 fatty acid epoxides produced by PAF-AH2 in mast cells regulate pulmonary vascular remodeling

Hidenori Moriyama, Jin Endo, Masaharu Kataoka, Yuta Shimanaka, Nozomu Kono, Yuki Sugiura, Shinichi Goto, Hiroki Kitakata, Takahiro Hiraide, Naohiro Yoshida, Sarasa Isobe, Tsunehisa Yamamoto, Kohsuke Shirakawa, Atsushi Anzai, Yoshinori Katsumata, Makoto Suematsu, Kenjiro Kosaki, Keiichi Fukuda, Hiroyuki Arai, Motoaki Sano

研究成果: Article査読

2 被引用数 (Scopus)

抄録

Pulmonary hypertension is a fatal rare disease that causes right heart failure by elevated pulmonary arterial resistance. There is an unmet medical need for the development of therapeutics focusing on the pulmonary vascular remodeling. Bioactive lipids produced by perivascular inflammatory cells might modulate the vascular remodeling. Here, we show that ω-3 fatty acid-derived epoxides (ω-3 epoxides) released from mast cells by PAF-AH2, an oxidized phospholipid-selective phospholipase A2, negatively regulate pulmonary hypertension. Genetic deletion of Pafah2 in mice accelerate vascular remodeling, resulting in exacerbation of hypoxic pulmonary hypertension. Treatment with ω-3 epoxides suppresses the lung fibroblast activation by inhibiting TGF-β signaling. In vivo ω-3 epoxides supplementation attenuates the progression of pulmonary hypertension in several animal models. Furthermore, whole-exome sequencing for patients with pulmonary arterial hypertension identifies two candidate pathogenic variants of Pafah2. Our findings support that the PAF-AH2-ω-3 epoxide production axis could be a promising therapeutic target for pulmonary hypertension.

本文言語English
論文番号3013
ジャーナルNature communications
13
1
DOI
出版ステータスPublished - 2022 12月

ASJC Scopus subject areas

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 一般
  • 物理学および天文学(全般)

フィンガープリント

「Omega-3 fatty acid epoxides produced by PAF-AH2 in mast cells regulate pulmonary vascular remodeling」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル