Lethal ventricular tachyarrhythmia (LVTA) is the most prevalent electrophysiological underpinning of sudden cardiac death (SCD), a condition that occurs in response to multiple pathophysiological abnormalities. The aim of this study was to identify common lipid features of LVTA that were induced by distinct pathophysiological conditions, thereby facilitating the discovery of novel SCD therapeutic targets. Two rat LVTA-SCD models were established to mimic myocardial infarction (MI) and myocardial ion channel diseases. Myocardial and serum specimens were analyzed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based lipidomics. The lipid profiles of the myocardial and serum specimens were similar between the models. Eleven myocardial lipid classes were altered, including downregulations of: cardiolipin, ceramide, phosphatidylinositol, phosphatidylethanolamine, triacylglycerol, diacylglycerol, phosphatidylglycerol, lysophosphatidylethanolamine and phosphatidylserine, and upregulations of: lysophosphatidylcholine and phosphatidic acid. Serum concentrations of triacylglycerol, lysophosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol were also altered. Alterations of lipids in paired myocardia and sera were closely correlated. Cardiolipin 70:5, cardiolipin 74:9 and ceramide d34:2 were tested as potential biomarkers of LVTA. The results indicate that there are common LVTA lipid profiles induced by MI and myocardial ion channel diseases, potentially offering novel LVTA-SCD therapeutic targets.

译文

:致命性室性心律失常(LVTA)是心脏猝死(SCD)的最普遍的电生理基础,这种情况是由于多种病理生理异常而引起的。这项研究的目的是确定由不同的病理生理条件诱导的LVTA的常见脂质特征,从而促进新的SCD治疗靶标的发现。建立了两种大鼠LVTA-SCD模型来模拟心肌梗塞(MI)和心肌离子通道疾病。使用基于超高效液相色谱-质谱(UPLC-MS)的脂质组学分析心肌和血清标本。在两个模型之间,心肌和血清标本的脂质谱相似。改变了11种心肌脂质的类别,包括下调:心磷脂,神经酰胺,磷脂酰肌醇,磷脂酰乙醇胺,三酰基甘油,二酰基甘油,磷脂酰甘油,溶血磷脂酰乙醇胺和磷脂酰丝氨酸,以及溶血磷脂酰磷酸的上调。血清三酰甘油,溶血磷脂酰胆碱,磷脂酰乙醇胺和磷脂酰肌醇的浓度也发生了改变。配对的心肌和血清中脂质的变化密切相关。心磷脂70:5,心磷脂74:9和神经酰胺d34:2被测试为LVTA的潜在生物标志物。结果表明存在由MI和心肌离子通道疾病引起的常见LVTA脂质谱,可能提供新的LVTA-SCD治疗靶标。

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