Atrial fibrillation (Afib) is the most common type of abnormal heart beat. It is characterized by scarring of the atrial region of the heart (a hallmark known as atrial fibrosis). Although atrial fibrosis is thought to perpetuate Afib, exactly how it develops has not been determined. Some research has suggested a role for inflammation in the process.
Consistent with this, a team of researchers led by Issei Komuro, at Chiba University Graduate School of Medicine, Japan, has now identified a role for immune cells known as mast cells in inducing atrial fibrosis and Afib in a mouse model of the condition.
The research appears in the Journal of Clinical Investigation.
Initial analysis indicated that in the mouse model of Afib, mast cells accumulate and become activated in the atria of the hearts, which are characterized by atrial fibrosis and enhanced susceptibility to induction of Afib. Stabilizing mast cells and generating mast cell-deficient mice reduced fibrotic atrial remodeling and susceptibility to Afib induction. Mechanistic studies determined that atrium-infiltrating mast cells increased production of the molecule PDGF-A and that this promoted atrial fibrosis and susceptibility to Afib induction.
The authors therefore suggest that targeting the mast cell/PDGF-A axis might provide a way to prevent Afib in stressed hearts, although they caution that further studies are needed to determine whether the same mechanism operates upstream of Afib in large animals.
- Chien-Hui Liao, Hiroshi Akazawa, Masaji Tamagawa, Kaoru Ito, Noritaka Yasuda, Yoko Kudo, Rie Yamamoto, Yukako Ozasa, Masanori Fujimoto, Ping Wang, Hiromitsu Nakauchi, Haruaki Nakaya and Issei Komuro. Cardiac mast cells cause atrial fibrillation through PDGF-A-mediated fibrosis in pressure-overloaded mouse hearts. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI39942
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