Long-term administration of pyridostigmine attenuates pressure overload-induced cardiac hypertrophy by inhibiting calcineurin signalling.
Long-term administration of pyridostigmine attenuates pressure overload-induced cardiac hypertrophy by inhibiting calcineurin signalling.
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长期服用吡斯的明通过抑制钙调磷酸酶信号传导来减轻压力超负荷引起的心脏肥大
DOI：
10.1111/jcmm.13133
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发表时间：
2017-09
影响因子：
5.3
通讯作者：
Zang WJ
中科院分区：
文献类型：
--
作者：
Lu Y;Zhao M;Liu JJ;He X;Yu XJ;Liu LZ;Sun L;Chen LN;Zang WJ
心脏肥大与自主神经失衡有关，其特征在于交感神经活动增强和副交感神经控制的撤销。增加副交感神经功能改善心室性能。然而，可逆性乙酰胆碱酯酶抑制剂吡啶斯的明是否可以抵消压力超负荷引起的心肌肥大仍不清楚。因此，本研究旨在确定吡啶斯的明是否可以改善压力超负荷诱导的心脏肥大，并确定其潜在机制。对大鼠进行假手术或腹主动脉缩窄手术，并用或不用吡啶斯的明治疗8周。使用PowerLab测定迷走神经活动和心功能。使用各种组织学染色评价心脏肥大。通过Western印迹和免疫沉淀定量心肌肥大的蛋白质标志物。压力超负荷导致迷走神经放电明显减少，心脏肥大指数和心功能不全显著增加。吡斯的明通过抑制乙酰胆碱酯酶而增加压力超负荷大鼠的乙酰胆碱水平。基于左心室重量/体重的降低、心房利钠肽、脑利钠肽和β-肌球蛋白重链水平的抑制以及心脏纤维化的减少，吡斯的明可显著减轻心脏肥大。这些效果伴随着心脏功能的显著改善。此外，吡啶斯的明抑制CaN/NFAT 3/GATA 4通路，并抑制Orai 1/STIM 1复合物的形成。总之，压力超负荷导致心脏肥大，心功能不全和迷走神经放电的显着减少。吡斯的明可减轻心肌肥厚并改善心功能，这与改善胆碱能传递效率（降低乙酰胆碱酯酶和增加乙酰胆碱）、抑制CaN/NFAT 3/GATA 4通路和抑制Orai 1/STIM 1相互作用有关。
Cardiac hypertrophy is associated with autonomic imbalance, characterized by enhanced sympathetic activity and withdrawal of parasympathetic control. Increased parasympathetic function improves ventricular performance. However, whether pyridostigmine, a reversible acetylcholinesterase inhibitor, can offset cardiac hypertrophy induced by pressure overload remains unclear. Hence, this study aimed to determine whether pyridostigmine can ameliorate pressure overload‐induced cardiac hypertrophy and identify the underlying mechanisms. Rats were subjected to either sham or constriction of abdominal aorta surgery and treated with or without pyridostigmine for 8 weeks. Vagal activity and cardiac function were determined using PowerLab. Cardiac hypertrophy was evaluated using various histological stains. Protein markers for cardiac hypertrophy were quantitated by Western blot and immunoprecipitation. Pressure overload resulted in a marked reduction in vagal discharge and a profound increase in cardiac hypertrophy index and cardiac dysfunction. Pyridostigmine increased the acetylcholine levels by inhibiting acetylcholinesterase in rats with pressure overload. Pyridostigmine significantly attenuated cardiac hypertrophy based on reduction in left ventricular weight/body weight, suppression of the levels of atrial natriuretic peptide, brain natriuretic peptide and β‐myosin heavy chain, and a reduction in cardiac fibrosis. These effects were accompanied by marked improvement of cardiac function. Additionally, pyridostigmine inhibited the CaN/NFAT3/GATA4 pathway and suppressed Orai1/STIM1 complex formation. In conclusion, pressure overload resulted in cardiac hypertrophy, cardiac dysfunction and a significant reduction in vagal discharge. Pyridostigmine attenuated cardiac hypertrophy and improved cardiac function, which was related to improved cholinergic transmission efficiency (decreased acetylcholinesterase and increased acetylcholine), inhibition of the CaN/NFAT3/GATA4 pathway and suppression of the interaction of Orai1/STIM1.
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DOI：
10.3109/17453678008990848
发表时间：
1980-01-01
期刊：
ACTA ORTHOPAEDICA SCANDINAVICA
影响因子：
--
作者：
ALLEN, HL;WASE, A;BEAR, WT
通讯作者：
BEAR, WT
影响因子：
5.7
作者：
Androne, AS;Hryniewicz, K;Katz, SD
通讯作者：
Katz, SD
影响因子：
10.8
作者：
Lopez-Olaneta, Marina M.;Villalba, Maria;Lara-Pezzi, Enrique
通讯作者：
Lara-Pezzi, Enrique
影响因子：
37.8
作者：
Hulot JS;Fauconnier J;Ramanujam D;Chaanine A;Aubart F;Sassi Y;Merkle S;Cazorla O;Ouillé A;Dupuis M;Hadri L;Jeong D;Mühlstedt S;Schmitt J;Braun A;Bénard L;Saliba Y;Laggerbauer B;Nieswandt B;Lacampagne A;Hajjar RJ;Lompré AM;Engelhardt S
通讯作者：
Engelhardt S
影响因子：
3.7
作者：
Gavioli M;Lara A;Almeida PW;Lima AM;Damasceno DD;Rocha-Resende C;Ladeira M;Resende RR;Martinelli PM;Melo MB;Brum PC;Fontes MA;Souza Santos RA;Prado MA;Guatimosim S
通讯作者：
Guatimosim S