Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, Heilongjiang 150081, People's Republic of China.
Naunyn Schmiedebergs Arch Pharmacol. 2012 Aug;385(8):823-31. doi: 10.1007/s00210-012-0740-4. Epub 2012 May 9.
Choline, an agonist of M(3) muscarinic acetylcholine receptors, is a precursor and metabolite of acetylcholine and is also a functional modulator of cellular membrane. However, the effect of choline on cardiac hypertrophy is not fully understood. The present study was therefore designed to explore whether choline could prevent cardiac hypertrophy induced by angiotensin II (Ang II) and clarify its potential mechanisms. Cardiac hypertrophy was induced by 0.6 mg kg(-1) day(-1) Ang II for 2 weeks in the presence or absence of choline pretreatment, while cardiomyocyte hypertrophy was induced by Ang II 0.1 μM for 48 h. We found that choline pretreatment attenuated the increment cell size of cardiomyocytes induced by Ang II both in vivo and in vitro. The high ANP and β-MHC levels induced by Ang II were also reversed by choline in cardiomyocytes. Meanwhile, choline pretreatment prevented the augment of reactive oxygen species (ROS) and intracellular calcium concentration in Ang II-treated cardiomyocytes. Furthermore, the upregulated phospho-p38 mitogen-activated protein kinase (MAPK) and calcineurin levels by Ang II in ventricular myocytes were attenuated by choline. In conclusion, choline prevents Ang II-induced cardiac hypertrophy through inhibition of ROS-mediated p38 MAPK activation as well as regulation of Ca(2+)-mediated calcineurin signal transduction pathway. Our results provide new insights into the pharmacological role of choline in cardiovascular diseases.
胆碱是 M3 毒蕈碱乙酰胆碱受体的激动剂，是乙酰胆碱的前体和代谢物，也是细胞膜的功能调节剂。然而，胆碱对心肌肥厚的影响尚不完全清楚。因此，本研究旨在探讨胆碱是否能预防血管紧张素 II（Ang II）诱导的心肌肥厚，并阐明其潜在的机制。在存在或不存在胆碱预处理的情况下，用 0.6mg/kg·d-1 Ang II 处理 2 周诱导心肌肥厚，用 0.1μM Ang II 处理 48h 诱导心肌细胞肥大。我们发现，胆碱预处理可减轻 Ang II 诱导的心肌细胞大小增加，无论是在体内还是体外。Ang II 诱导的高 ANP 和β-MHC 水平也被胆碱在心肌细胞中逆转。同时，胆碱预处理可防止 Ang II 处理的心肌细胞中活性氧（ROS）和细胞内钙浓度的增加。此外，胆碱可减轻 Ang II 上调的心肌细胞中磷酸化 p38 丝裂原活化蛋白激酶（p38 MAPK）和钙调神经磷酸酶水平。总之，胆碱通过抑制 ROS 介导的 p38 MAPK 激活以及调节 Ca2+ 介导的钙调神经磷酸酶信号转导通路来预防 Ang II 诱导的心肌肥厚。我们的研究结果为胆碱在心血管疾病中的药理学作用提供了新的见解。
