Abstract:
Arrhythmogenic cardiomyopathy (ACM) is a familial heart disease characterized by cardiac dysfunction, arrhythmias, and myocardial inflammation. Exercise and stress can influence the disease\'s progression. Thus, an investigation of whether a high-fat diet (HFD) contributes to ACM pathogenesis is warranted. In a robust ACM mouse model, 8-week-old Desmoglein-2 mutant (Dsg2mut/mut) mice were fed either an HFD or rodent chow for 8 weeks. Chow-fed wildtype (WT) mice served as controls. Echo- and electrocardiography images pre- and post-dietary intervention were obtained, and the lipid burden, inflammatory markers, and myocardial fibrosis were assessed at the study endpoint. HFD-fed Dsg2mut/mut mice showed numerous P-wave perturbations, reduced R-amplitude, left ventricle (LV) remodeling, and reduced ejection fraction (%LVEF). Notable elevations in plasma high-density lipoprotein (HDL) were observed, which correlated with the %LVEF. The myocardial inflammatory adipokines, adiponectin (AdipoQ) and fibroblast growth factor-1, were substantially elevated in HFD-fed Dsg2mut/mut mice, albeit no compounding effect was observed in cardiac fibrosis. The HFD not only potentiated cardiac dysfunction but additionally promoted adverse cardiac remodeling. Further investigation is warranted, particularly given elevated AdipoQ levels and the positive correlation of HDL with the %LVEF, which may suggest a protective effect. Altogether, the HFD worsened some, but not all, disease phenotypes in Dsg2mut/mut mice. Notwithstanding, diet may be a modifiable environmental factor in ACM disease progression.
摘要:
心律失常性心肌病(ACM)是一种以心功能不全为特征的家族性心脏病,心律失常,和心肌炎症。运动和压力可以影响疾病的进展。因此,有必要研究高脂饮食(HFD)是否有助于ACM发病机制.在健壮的ACM小鼠模型中,给8周龄的Desmoglein-2突变体(Dsg2mut/mut)小鼠喂食HFD或啮齿动物食物8周。Chow饲喂的野生型(WT)小鼠作为对照。获得饮食干预前后的回声和心电图图像,和脂质负担,炎症标志物,和心肌纤维化在研究终点进行评估。HFD喂养的Dsg2mut/mut小鼠显示出许多P波扰动,减小的R振幅,左心室(LV)重塑,降低射血分数(%LVEF)。观察到血浆高密度脂蛋白(HDL)显著升高,与%LVEF相关。心肌炎症脂肪因子,脂联素(AdipoQ)和成纤维细胞生长因子-1,在HFD喂养的Dsg2mut/mut小鼠中显著升高,尽管在心脏纤维化中未观察到复合效应。HFD不仅增强了心脏功能障碍,而且还促进了不良的心脏重塑。需要进一步调查,特别是考虑到AdipoQ水平升高和HDL与%LVEF呈正相关,这可能表明有保护作用。总之,HFD恶化了一些,但不是全部,Dsg2mut/mut小鼠的疾病表型。尽管如此,饮食可能是ACM疾病进展中的一个可改变的环境因素。