Department of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, Germany.
DZHK (German Centre for Cardiovascular Research), 17475 Greifswald, Germany.
Int J Mol Sci. 2021 Feb 18;22(4):1999. doi: 10.3390/ijms22041999.
With more than 25 million people affected, heart failure (HF) is a global threat. As energy production pathways are known to play a pivotal role in HF, we sought here to identify key metabolic changes in ischemic- and non-ischemic HF by using a multi-OMICS approach. Serum metabolites and mRNAseq and epigenetic DNA methylation profiles were analyzed from blood and left ventricular heart biopsy specimens of the same individuals. In total we collected serum from = 82 patients with Dilated Cardiomyopathy (DCM) and = 51 controls in the screening stage. We identified several metabolites involved in glycolysis and citric acid cycle to be elevated up to 5.7-fold in DCM ( = 1.7 × 10). Interestingly, cardiac mRNA and epigenetic changes of genes encoding rate-limiting enzymes of these pathways could also be found and validated in our second stage of metabolite assessment in = 52 DCM, = 39 ischemic HF and = 57 controls. In conclusion, we identified a new set of metabolomic biomarkers for HF. We were able to identify underlying biological cascades that potentially represent suitable intervention targets.
受影响的人数超过 2500 万，心力衰竭（HF）是一个全球性的威胁。由于能量产生途径已知在 HF 中起着关键作用，我们在这里试图通过多组学方法来确定缺血性和非缺血性 HF 的关键代谢变化。从同一个体的血液和左心室心脏活检标本中分析了血清代谢物和 mRNAseq 和表观遗传 DNA 甲基化谱。在筛选阶段，我们共收集了 82 例扩张型心肌病（DCM）患者和 51 名对照者的血清。我们发现了一些涉及糖酵解和柠檬酸循环的代谢物，在 DCM 中升高了 5.7 倍（ = 1.7 × 10）。有趣的是，在我们对 52 例 DCM、39 例缺血性 HF 和 57 例对照者的第二次代谢物评估中，也可以发现和验证编码这些途径限速酶的心脏 mRNA 和表观遗传变化。总之，我们确定了一组新的 HF 代谢组学生物标志物。我们能够确定潜在的生物学级联反应，这些级联反应可能代表合适的干预靶点。
