Transient receptor potential vanilloid 1-expressing cardiac afferent nerves may contribute to cardiac hypertrophy in accompany with an increased expression of brain-derived neurotrophic factor within nucleus tractus solitarius in a pressure overload model
Transient receptor potential vanilloid 1-expressing cardiac afferent nerves may contribute to cardiac hypertrophy in accompany with an increased expression of brain-derived neurotrophic factor within nucleus tractus solitarius in a pressure overload model
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DOI：
10.1080/10641963.2022.2029470
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发表时间：
2022-01
影响因子：
12.3
通讯作者：
R. Shibata;Keisuke Shinohara;S. Ikeda;Takeshi Iyonaga;Taku Matsuura;Soichiro Kashihara;Koji Ito;T. Kishi;Y. Hirooka;H. Tsutsui
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作者：
R. Shibata;Keisuke Shinohara;S. Ikeda;Takeshi Iyonaga;Taku Matsuura;Soichiro Kashihara;Koji Ito;T. Kishi;Y. Hirooka;H. Tsutsui
交感神经输出增加导致心脏肥厚。交感神经兴奋是通过心脏传入末梢的瞬时受体电位香草蛋白1 （TRPV1）激活心脏交感传入神经而引起的。脑干孤束核（NTS）接受感觉心脏传入输入。脑源性神经营养因子（BDNF）在NTS内以活动依赖的方式从感觉神经元释放。此外，NTS中的BDNF还能调节交感神经活动。因此，我们假设在NTS中，表达trpv1的心脏传入神经在BDNF表达增加的同时有助于心脏肥厚。方法与结果采用野生型C57BL/6 J （WT-AB）和TRPV1基因敲除小鼠（TRPV1 KO-AB）进行腹主动脉束带（AB）或假手术。术后8周，WT-AB小鼠的超声心动图左室壁厚度和心脏重量/体重比明显大于WT-Sham小鼠，TRPV1 KO-AB小鼠的这些肥厚指标均有所减轻。各组间左心室缩短率无明显差异。与WT-Sham小鼠相比，WT-AB小鼠心脏中TRPV1和NTS中BDNF的蛋白水平显著升高，而TRPV1- ko小鼠NTS中BDNF的表达未因AB而升高。化学消融术治疗表达trpv1的心肌梗死，可减轻ab诱导的心肌肥厚，并降低NTS中BDNF的升高。使用心率变异性分析交感神经活动，与WT-Sham小鼠相比，WT-AB小鼠对心脏传入刺激的交感神经兴奋反应增加。结论trpv1表达的心脏传入神经可能参与了NTS内BDNF升高引起的压力过载引起的心脏肥厚。
ABSTRACT Introduction Increased sympathetic output contributes to cardiac hypertrophy. Sympathoexcitation is induced by activating the cardiac sympathetic afferent nerves through transient receptor potential vanilloid 1 (TRPV1) in cardiac afferent endings. Brainstem nucleus tractus solitarius (NTS) receives the sensory cardiac afferent inputs. Brain-derived neurotrophic factor (BDNF) is released within NTS from sensory neurons in an activity-dependent manner. Additionally, BDNF in NTS tonically regulates sympathetic activity. Therefore, we hypothesized that TRPV1-expressing cardiac afferent nerves contribute to cardiac hypertrophy in accompany with an increased BDNF expression in NTS. Methods and Results Abdominal aortic banding (AB) or sham operation was conducted in wild-type C57BL/6 J (WT-AB) and TRPV1 knockout mice (TRPV1 KO-AB). At 8 weeks post-operation, echocardiographic left ventricular wall thickness and heart weight/body weight ratio were significantly greater in WT-AB than WT-Sham mice, and these hypertrophic indexes were attenuated in TRPV1 KO-AB mice. Among the groups, left ventricular fractional shortening was not different. The protein levels of TRPV1 in heart and BDNF in NTS were significantly increased in WT-AB compared to WT-Sham mice, whereas BDNF expression in NTS was not increased by AB in TRPV1-KO mice. Chemical ablation of TRPV1-expressing cardiac afferents attenuated the AB-induced cardiac hypertrophy and increase in BDNF in NTS. Sympathetic activity analyzed using heart rate variability, and sympathoexcitatory responses to the stimulation of cardiac afferents were increased in WT-AB compared to WT-Sham mice. Conclusion TRPV1-expressing cardiac afferent nerves may contribute to pressure overload-induced cardiac hypertrophy in accompany with the increased BDNF within NTS.