Toll-Like Receptor 9 Promotes Survival in SERCA2a KO Heart Failure Mice

作者：Dhondup Yangchen; Sjaastad Ivar; Sandanger Oystein; Aronsen Jan Magnus; Ahmed Muhammad Shakil; Attramadal Havard; Finsen Alexandra Vanessa; Zhang Lili; Ranheim Trine; Alfsnes Katrine; Aukrust Pal; Christensen Geir; Yndestad Arne; Vinge Leif Erik

来源：Mediators of Inflammation, 2017, 2017: 9450439.

DOI：10.1155/2017/9450439

Aim. Inflammation is important in heart failure (HF). The role of the immune receptor toll-like receptor 9 (TLR9) in HF is not understood and not investigated in diastolic HF. We investigated the role of TLR9 in a murine diastolic HF model caused by cardiomyocyte SERCA2a excision. Methods and Results. We crossed SERCA2a KO and TLR9 KO mice to generate four mouse lines. Tamoxifen-induced cardiomyocyte SERCA2a gene excision was carried out in mice, causing diastolic HF. After 7.6 weeks, cardiac functions and dimensions were analyzed by echocardiography and heart tissues were processed. HF mice depleted of TLR9 demonstrated reduced survival compared to SERC2a KO mice, with a median life expectancy of 58 days compared to 63 days. Both HF groups displayed increased left atrium size, lung weight, fetal gene expressions, monocyte/macrophage infiltration, and fibrosis. However, there were no significant differences between the groups. Conclusion. In mice with SERCA2a KO-induced diastolic HF, the absence of TLR9 reduced median life expectancy. The cause remains elusive, as all investigated HF parameters were unaltered. Still, these findings support a salutary role of TLR9 in some subsets of HF conditions and underline the importance for future studies on the mechanisms of TLR9 in diastolic HF.

• 出版日期2017