Chauhan Pankaj Kumar, Sowdhamini Ramanathan
National Centre for Biological Sciences (Tata Institute of Fundamental Research), Bangalore, India.
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
Front Cardiovasc Med. 2023 May 23;10:1110119. doi: 10.3389/fcvm.2023.1110119. eCollection 2023.
Cardiomyopathies are complex heart diseases with significant prevalence around the world. Among these, primary forms are the major contributors to heart failure and sudden cardiac death. As a high-energy demanding engine, the heart utilizes fatty acids, glucose, amino acid, lactate and ketone bodies for energy to meet its requirement. However, continuous myocardial stress and cardiomyopathies drive towards metabolic impairment that advances heart failure (HF) pathogenesis. So far, metabolic profile correlation across different cardiomyopathies remains poorly understood.
In this study, we systematically explore metabolic differences amongst primary cardiomyopathies. By assessing the metabolic gene expression of all primary cardiomyopathies, we highlight the significantly shared and distinct metabolic pathways that may represent specialized adaptations to unique cellular demands. We utilized publicly available RNA-seq datasets to profile global changes in the above diseases (|| ≥ 0.28 and BH 0.1) and performed gene set analysis (GSA) using the PAGE statistics on KEGG pathways.
Our analysis demonstrates that genes in arachidonic acid metabolism (AA) are significantly perturbed across cardiomyopathies. In particular, the arachidonic acid metabolism gene interacts with fibroblast marker genes and can potentially influence fibrosis during cardiomyopathy.
The profound significance of AA metabolism within the cardiovascular system renders it a key player in modulating the phenotypes of cardiomyopathies.
心肌病是复杂的心脏疾病，在全球范围内具有较高的患病率。其中，原发性心肌病是导致心力衰竭和心源性猝死的主要原因。作为一个对能量需求很高的器官，心脏利用脂肪酸、葡萄糖、氨基酸、乳酸和酮体来获取能量以满足其需求。然而，持续的心肌应激和心肌病会导致代谢受损，进而推动心力衰竭（HF）的发病机制。到目前为止，不同心肌病之间的代谢特征相关性仍知之甚少。
在本研究中，我们系统地探讨了原发性心肌病之间的代谢差异。通过评估所有原发性心肌病的代谢基因表达，我们突出了显著共享和独特的代谢途径，这些途径可能代表了对独特细胞需求的特殊适应性。我们利用公开可用的RNA测序数据集来描绘上述疾病中的全局变化（||≥0.28且BH 0.1），并使用KEGG途径上的PAGE统计进行基因集分析（GSA）。
我们的分析表明，花生四烯酸代谢（AA）中的基因在各种心肌病中均受到显著干扰。特别是，花生四烯酸代谢基因与成纤维细胞标记基因相互作用，并可能在心肌病期间影响纤维化。
AA代谢在心血管系统中的深远意义使其成为调节心肌病表型的关键因素。
