Fibroblasts are the most numerous cell type in the heart, but they are considered to have a less important role in heart failure than heart muscle cells. However, a team of researchers, at the University of Tokyo Graduate School of Medicine, Japan, has now determined that fibroblasts are essential for the response of the mouse heart to conditions that mimic high blood pressure, a response that if sustained ultimately leads to heart failure.
The research appears in the Journal of Clinical Investigation.
The team, led by Ryozo Nagai and Ichiro Manabe, showed that mice lacking Klf5 only in heart muscle cells mounted a normal response to conditions designed to mimic moderate increases in blood pressure, whereas mice lacking Klf5 only in fibroblasts in the heart failed to respond to such conditions. Surprisingly, mice lacking Klf5 only in fibroblasts in the heart developed more severe heart failure than normal mice and died when subjected to conditions designed to mimic extreme increases in blood pressure.
The authors therefore conclude that fibroblasts in the heart have a central role in the response of the heart to changes in blood pressure and suggest that modulating their function might provide a way to treat individuals with heart failure.
- Norifumi Takeda, Ichiro Manabe, Yuichi Uchino, Kosei Eguchi, Sahohime Matsumoto, Satoshi Nishimura, Takayuki Shindo, Motoaki Sano, Kinya Otsu, Paige Snider, Simon J. Conway and Ryozo Nagai. Cardiac fibroblasts are essential for the adaptive response of the murine heart to pressure overload. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI40295
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