动脉粥样硬化会加剧心肌梗死后的心律失常：心肌炎症的作用。
Atherosclerosis exacerbates arrhythmia following myocardial infarction: Role of myocardial inflammation.
作者信息
De Jesus Nicole M, Wang Lianguo, Herren Anthony W, Wang Jingjing, Shenasa Fatemah, Bers Donald M, Lindsey Merry L, Ripplinger Crystal M
机构信息
Department of Pharmacology, University of California, Davis, School of Medicine, Davis, California; Department of Biomedical Engineering, University of California, Davis, School of Engineering, Davis, California.
Department of Pharmacology, University of California, Davis, School of Medicine, Davis, California.
出版信息
Heart Rhythm. 2015 Jan;12(1):169-78. doi: 10.1016/j.hrthm.2014.10.007. Epub 2014 Oct 7.
BACKGROUND
Atherosclerotic animal models show increased recruitment of inflammatory cells to the heart after myocardial infarction (MI), which impacts ventricular function and remodeling.
OBJECTIVE
The purpose of this study was to determine whether increased myocardial inflammation after MI also contributes to arrhythmias.
METHODS
MI was created in 3 mouse models: (1) atherosclerotic (apolipoprotein E deficient [ApoE(-/-)] on atherogenic diet, n = 12); (2) acute inflammation (wild-type [WT] given daily lipopolysaccharide [LPS] 10 μg/day, n = 7); and (3) WT (n = 14). Sham-operated (n = 4) mice also were studied. Four days post-MI, an inflammatory protease-activatable fluorescent probe (Prosense680) was injected intravenously to quantify myocardial inflammation on day 5. Optical mapping with voltage-sensitive dye was performed on day 5 to assess electrophysiology and arrhythmia susceptibility.
RESULTS
Inflammatory activity (Prosense680 fluorescence) was increased approximately 2-fold in ApoE+MI and LPS+MI hearts vs WT+MI (P<.05) and 3-fold vs sham (P<.05). ApoE+MI and LPS+MI hearts also had prolonged action potential duration, slowed conduction velocity, and increased susceptibility to pacing-induced arrhythmias (56% and 71% vs 13% for WT+MI and 0% for sham, respectively, P<.05, for ApoE+MI and LPS+MI groups vs both WT+MI and sham). Increased macrophage accumulation in ApoE+MI and LPS+MI hearts was confirmed by immunofluorescence. Macrophages were associated with areas of connexin43 (Cx43) degradation, and a 2-fold decrease in Cx43 expression was found in ApoE+MI vs WT+MI hearts (P<.05). ApoE+MI hearts also had a 3-fold increase in interleukin-1β expression, an inflammatory cytokine known to degrade Cx43.
CONCLUSION
Underlying atherosclerosis exacerbates post-MI electrophysiological remodeling and arrhythmias. LPS+MI hearts fully recapitulate the atherosclerotic phenotype, suggesting myocardial inflammation as a key contributor to post-MI arrhythmia.
背景
动脉粥样硬化动物模型显示，心肌梗死（MI）后心脏中炎症细胞的募集增加，这会影响心室功能和重塑。
目的
本研究旨在确定MI后心肌炎症增加是否也会导致心律失常。
方法
在3种小鼠模型中制造MI：（1）动脉粥样硬化模型（喂食致动脉粥样硬化饮食的载脂蛋白E缺陷型[ApoE(-/-)]小鼠，n = 12）；（2）急性炎症模型（野生型[WT]小鼠每日给予10 μg脂多糖[LPS]，n = 7）；（3）WT小鼠（n = 14）。还研究了假手术小鼠（n = 4）。MI后4天，静脉注射一种炎症蛋白酶激活荧光探针（Prosense680），以在第5天定量心肌炎症。在第5天进行电压敏感染料光学标测，以评估电生理和心律失常易感性。
结果
与WT+MI组相比，ApoE+MI组和LPS+MI组心脏的炎症活性（Prosense680荧光）增加约2倍（P<0.05），与假手术组相比增加3倍（P<0.05）。ApoE+MI组和LPS+MI组心脏的动作电位时程也延长，传导速度减慢，起搏诱导的心律失常易感性增加（ApoE+MI组和LPS+MI组分别为56%和71%，而WT+MI组为13%，假手术组为0%，ApoE+MI组和LPS+MI组与WT+MI组和假手术组相比，P<0.05）。免疫荧光证实ApoE+MI组和LPS+MI组心脏中巨噬细胞积聚增加。巨噬细胞与连接蛋白43（Cx43）降解区域相关，与WT+MI组心脏相比，ApoE+MI组心脏中Cx43表达降低2倍（P<0.05）。ApoE+MI组心脏中白细胞介素-1β表达也增加3倍，白细胞介素-1β是一种已知可降解Cx43的炎症细胞因子。
结论
潜在的动脉粥样硬化会加剧MI后的电生理重塑和心律失常。LPS+MI组心脏完全重现了动脉粥样硬化表型，提示心肌炎症是MI后心律失常的关键因素。
Zotero 插件