Department of Clinical Science and Services, Royal Veterinary College, University of London, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire, AL9 7TA, London, United Kingdom.
Research Support Office, Royal Veterinary College, University of London, London, United Kingdom.
Metabolomics. 2022 May 30;18(6):34. doi: 10.1007/s11306-022-01887-7.
Myxomatous mitral valve disease (MMVD) is the most common cardiac condition in adult dogs. The disease progresses over several years and affected dogs may develop congestive heart failure (HF). Research has shown that myocardial metabolism is altered in cardiac disease, leading to a reduction in β-oxidation of fatty acids and an increased dependence upon glycolysis.
This study aimed to evaluate whether a shift in substrate use occurs in canine patients with MMVD; a naturally occurring model of human disease.
Client-owned dogs were longitudinally evaluated at a research clinic in London, UK and paired serum samples were selected from visits when patients were in ACVIM stage B1: asymptomatic disease without cardiomegaly, and stage C: HF. Samples were processed using ultra-performance liquid chromatography mass spectrometry and lipid profiles were compared using mixed effects models with false discovery rate adjustment. The effect of disease stage was evaluated with patient breed entered as a confounder. Features that significantly differed were screened for selection for annotation efforts using reference databases.
Dogs in HF had altered concentrations of lipid species belonging to several classes previously associated with cardiovascular disease. Concentrations of certain acylcarnitines, phospholipids and sphingomyelins were increased after individuals had developed HF, whilst some ceramides and lysophosphatidylcholines decreased.
The canine metabolome appears to change as MMVD progresses. Findings from this study suggest that in HF myocardial metabolism may be characterised by reduced β-oxidation. This proposed explanation warrants further research.
黏液样心肌二尖瓣病（MMVD）是成年犬中最常见的心脏疾病。该疾病会在数年内逐渐发展，患病犬可能会发展为充血性心力衰竭（HF）。研究表明，心肌代谢在心脏疾病中发生改变，导致脂肪酸的β-氧化减少，糖酵解的依赖性增加。
本研究旨在评估犬 MMVD 患者（一种自然发生的人类疾病模型）是否存在底物利用的转变。
在英国伦敦的一家研究诊所对客户所有的犬进行纵向评估，并从患者处于 ACVIM 阶段 B1（无症状疾病且无心脏肿大）和阶段 C（HF）的就诊时选择配对的血清样本。使用超高效液相色谱-质谱联用技术对样本进行处理，并使用具有虚假发现率调整的混合效应模型比较脂质谱。使用患者品种作为混杂因素评估疾病阶段的影响。使用参考数据库对显著差异的特征进行筛选，以便进行注释工作。
HF 犬的几种先前与心血管疾病相关的脂质种类的浓度发生了改变。在个体发生 HF 后，某些酰基肉碱、磷脂和神经鞘磷脂的浓度增加，而某些神经酰胺和溶血磷脂酰胆碱的浓度降低。
随着 MMVD 的进展，犬的代谢组似乎发生了变化。本研究的结果表明，在 HF 中，心肌代谢可能以减少的β-氧化为特征。这一假设需要进一步研究。
