Metabonomics Analysis of Myocardial Metabolic Dysfunction in Patients with Cardiac Natriuretic Peptide Resistance

Abstract

Brain natriuretic peptide (BNP) is an important biological marker and regulator of cardiac function. BNP resistance is characterized by high concentrations of less functionally effective BNP and common in heart failure (HF) patients. However, the roles and consequences of BNP resistance remain poorly understood. Investigate the effects of cardiac BNP resistance and identify potential metabolic biomarkers for screening and diagnosis. Thirty patients and thirty healthy subjects were enrolled in this study. Cardiac functions were evaluated by echocardiography. The plasma levels of cyclic guanosine monophosphate (cGMP) and BNP were measured by enzyme-linked immunosorbent assay (ELISA) and the cGMP/BNP ratio is calculated to determine cardiac natriuretic peptide resistance. Liquid chromatograph tandem mass spectrometry (LC-MS) based untargeted metabolomics analysis was applied to screen metabolic changes. The cGMP/BNP ratio was markedly lower in HF patients than controls. The cGMP/BNP ratio and ejection fraction (EF) were strongly correlated (R2 = 0.676, P < 0.05 ). Importantly, metabolic profiles were substantially different between HF patients and healthy controls. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that the differentially expressed metabolites are involved in signaling pathways that regulate cardiac functions. In HF patients, BNP resistance develops in association with a reduction in heart function and metabolic remodeling. It suggests possible functional roles of BNP resistance in the regulation of cardiac metabolism.

The landscape of N6-methyladenosine modification patterns and altered transcript profiles in the cardiac-specific deletion of natriuretic peptide receptor A

“…In fact, 9 of the top 10 terms are associated with the metabolic process which is in good agreement with our past findings that NPs may play a pivotal role in metabolic functions. [27][28][29] Bubble plots show these metabolic processes in BP bars, the bubble size shows the counts of genes, the number of enriched genes are listed in brackets on the left, and the color of the bubble represents the P-value.…”

“…47 More importantly, we are highly concerned with the possible functional roles of NPRA and BNP resistance in the regulation of cardiac metabolism. 28,29 BNP resistance is characterized by high concentrations of less functionally effective BNP and is common in heart failure (HF) patients. Our previous result showed that NPRA-deficient mice have distinct metabolic patterns compared with control mice but the molecular mechanism that could account for this observation remains to be investigated.…”

“…28 Besides, distinguished altered metabolites were also found in HF patients with a remarkably lower cGMP/BNP ratio. 29 However, the molecular mechanism that could account for this observation induced by disabled natriuretic peptide signalling remains to be investigated.…”

Dietary Management of Heart Failure: DASH Diet and Precision Nutrition Perspectives

“…The medical literature includes multiple studies associating metabolites with HF characteristics and outcomes. Examples include findings that metabolic profiling can discriminate and identify patients at risk of HF-related decompensation, and metabolomic profiles showing differentially expressed signaling pathways are associated with lower cyclic guanosine monophosphate/brain natriuretic peptide (cGMP/BNP) ratios in HF patients [77,78]. Of relevance to the diet and gut health relationship, the gut-related metabolite trimethylamine N-oxide (TMAO) is associated with acute and long-term adverse outcomes in HF [79].…”