KLF2 mediates enhanced chemoreflex sensitivity, disordered breathing and autonomic dysregulation in heart failure
KLF2 mediates enhanced chemoreflex sensitivity, disordered breathing and autonomic dysregulation in heart failure
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DOI：
10.1113/jp273805
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发表时间：
2018-08-01
影响因子：
5.5
通讯作者：
Schultz, Harold D.
中科院分区：
文献类型：
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作者：
Marcus, Noah J.;Del Rio, Rodrigo;Schultz, Harold D.
振荡呼吸和交感神经活动（SNA）增加与心律失常发生率增加有关，并导致慢性心力衰竭（CHF）的死亡率。颈动脉体化学反射 (CBC) 敏感性的增加在此过程中发挥作用，并且可以由慢性血流量减少引起。我们假设剪切应力敏感转录因子 Kruppel 样因子 2 (KLF2) 的下调会介导 CHF 中 CBC 敏感性的增加，并导致相关的自主神经、呼吸和心脏后遗症。在假兔和 CHF 兔的休息时和 CBC 激活期间测量通气 (Ve)、肾 SNA (RSNA) 和心电图。振荡呼吸被量化为呼吸暂停低通气指数（AHI）和呼吸频率变异指数（RRVI）。静息状态下 CHF (FIO2 21%) 时，AHI（对照 61/h，CHF 251/h）、RRVI（对照 93/h，CHF 293/h）、RSNA（对照 222% max，CHF 435% max）和心律失常发生率（对照 50 +/- 10/h，CHF 300 +/- 100/h）增加，CBC 也是如此对 10% F-IO2 的反应（Ve、RSNA）（所有 P
Oscillatory breathing and increased sympathetic nerve activity (SNA) are associated with increased arrhythmia incidence and contribute to mortality in chronic heart failure (CHF). Increased carotid body chemoreflex (CBC) sensitivity plays a role in this process and can be precipitated by chronic blood flow reduction. We hypothesized that downregulation of a shear stress-sensitive transcription factor, Kruppel-like Factor 2 (KLF2), mediates increased CBC sensitivity in CHF and contributes to associated autonomic, respiratory and cardiac sequelae. Ventilation (Ve), renal SNA (RSNA) and ECG were measured at rest and during CBC activation in sham and CHF rabbits. Oscillatory breathing was quantified as the apnoea-hypopnoea index (AHI) and respiratory rate variability index (RRVI). AHI (control 61/h, CHF 251/h), RRVI (control 93/h, CHF 293/h), RSNA (control 222% max, CHF 435% max) and arrhythmia incidence (control 50 +/- 10/h, CHF 300 +/- 100/h) were increased in CHF at rest (FIO2 21%), as were CBC responses (Ve, RSNA) to 10% F-IO2 (all P