期刊
JOURNAL OF PHARMACOLOGICAL SCIENCES
卷 120, 期 4, 页码 296-304出版社
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1254/jphs.12202FP
关键词
atrial fibrillation; inflammation; macrophage; ATP; gap-junction channel
资金
- Program for Improvement of Research Environment for Young Researchers from Special Coordination Funds for Promoting Science and Technology (SCF)
- Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan [23390205]
- Japan Research Promotion Society for Cardiovascular Diseases
- Japan Heart Foundation/Novartis Grant for Research Award on Molecular and Cellular Cardiology
- Grants-in-Aid for Scientific Research [23390205] Funding Source: KAKEN
Atrial inflammation is critical to atrial fibrillation initiation and progression. Although left atrial dilatation is a risk factor for atrial fibrillation, the mechanism linking atrial dilatation and inflammation is unclear. We evaluated the mechanisms underlying infiltration of macrophages induced by stretch of atrial myocytes. Murine macrophages were co-cultured with HL-1 murine atrial myocyte derived cells. Mechanical stretch applied to atrial myocytes induced transwell macrophage migration. The gap junction channel blocker carbenoxolone and the non-specific ATP-signaling modifiers apyrase and pyridoxal-phosphate-6-azopheny1-2',4'-disulfonate inhibited the enhanced migration. Mechanical stretch of atrial myocytes induced transient increase in extracellular ATP concentration, which was inhibited by carbenoxolone. siRNA knockdown of pannexin-2 inhibited ATP release and macrophage migration. Mice underwent transverse aortic constriction or sham procedure. Transverse aortic constriction procedure induced macrophage infiltration. Daily carbenoxolone administration significantly inhibited macrophage infiltration in the atrium. Thus, mechanical stretch of atrial myocytes induces macrophage migration by ATP released through gap-junction channels, at least in part, in vitro. Administering a gap junction family channel blocker inhibited this inflammatory change in vivo.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据