慢性癌抑素治疗通过改善心肌梗死后心力衰竭大鼠的钙处理来降低心房颤动易感性。
Chronic catestatin treatment reduces atrial fibrillation susceptibility via improving calcium handling in post-infarction heart failure rats.
作者信息
Yan Min, Liu Tao, Zhong Peng, Xiong Feng, Cui Bo, Wu Jinchun, Wu Gang
机构信息
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China.
出版信息
Peptides. 2023 Jan;159:170904. doi: 10.1016/j.peptides.2022.170904. Epub 2022 Nov 12.
BACKGROUND
Abnormal Ca handling is a pivotal element of atrial fibrillation (AF) substrates. Catestatin (CST) modulates intracellular Ca handling in cardiomyocytes (CMs). We investigated the effects of CST administration on atrial Ca handling and AF susceptibility in rats with post-infarction heart failure (HF).
METHODS
Myocardial infarction (MI) was established by ligation of the left anterior descending coronary artery in rats. Two-week later, rats with post-infarction HF were randomly treated with saline (MI group) or CST (MI + CST group) for 4-week. Cellular Ca imaging was performed by incubating atrial CMs with Fura-2 AM. An in vitro electrophysiological study was performed to assess the vulnerability to action potential duration (APD) alternans and AF. Ca handling proteins expression was determined using western blotting.
RESULTS
In atrial CMs, compared with the sham group, the sarcoplasmic reticulum (SR) Ca load, Ca transient (CaT) amplitude, and threshold for Ca alternans were significantly decreased, but the diastolic intracellular Ca level, SR Ca leakage, and spontaneous Ca events were markedly increased in the MI group. However, CST attenuated these Ca-handling abnormalities induced by post-infarction HF. Moreover, vulnerability to atrial APD alternans and AF was significantly increased in isolated hearts from the MI group compared to the sham group, whereas all effects were prevented by CST. CST treatment also preserved SR Ca-ATPase protein expression but decreased the protein levels of phosphorylated-ryanodine receptor 2 and phosphorylated-Ca/calmodulin-dependent protein kinase II in atria from post-infarction HF rats.
CONCLUSION
Chronic CST treatment reduces AF vulnerability in rats with MI-induced HF by improving Ca handling.
背景
钙处理异常是心房颤动（AF）基质的关键要素。抑癌素（CST）可调节心肌细胞（CMs）内的钙处理。我们研究了给予CST对心肌梗死后心力衰竭（HF）大鼠心房钙处理及AF易感性的影响。
方法
通过结扎大鼠左冠状动脉前降支建立心肌梗死（MI）模型。两周后，将心肌梗死后HF大鼠随机分为生理盐水组（MI组）或CST组（MI + CST组），治疗4周。用Fura-2 AM孵育心房CMs进行细胞钙成像。进行体外电生理研究以评估动作电位时程（APD）交替和AF的易感性。用蛋白质印迹法测定钙处理蛋白的表达。
结果
在心房CMs中，与假手术组相比，MI组肌浆网（SR）钙负荷、钙瞬变（CaT）幅度和钙交替阈值显著降低，但舒张期细胞内钙水平、SR钙泄漏和自发性钙事件明显增加。然而，CST减轻了心肌梗死后HF诱导的这些钙处理异常。此外，与假手术组相比，MI组离体心脏对心房APD交替和AF的易感性显著增加，而CST可预防所有这些影响。CST治疗还保留了SR钙ATP酶蛋白表达，但降低了心肌梗死后HF大鼠心房中磷酸化兰尼碱受体2和磷酸化钙/钙调蛋白依赖性蛋白激酶II的蛋白水平。
结论
慢性CST治疗可通过改善钙处理降低MI诱导的HF大鼠的AF易感性。
Zotero 插件