Abstract
Purpose: Metabolic impairment is one key contributor to heart failure (HF) pathogenesis and progression. The major causes of HF, coronary heart disease (CHD), dilated cardiomyopathy (DCM), and valvular heart disease (VHD) remains poorly characterized in patients with HF from the view of metabolic profile. We sought to determine metabolic differences in CHD-, VHD-, and DCM-induced HF patients and identify significantly altered metabolites and their correlations.Procedure: In this study, a total of 96 HF cases and 97 controls were enrolled. The contents of 23 amino acids and 26 carnitines in fasting plasma were measured by a targeted liquid chromatography and mass spectrometry (LC-MS) approach.Results: Nine metabolites (Histidine, Arginine, Citrulline, Glutamine, Valine, hydroxyhexadecenyl-carnitine, acylcarnitine C22, hydroxytetradecanoyl-carnitine, and carnitine) were found to be related with the occurrence of HF. Arginine, Glutamine and hydroxytetradecanoyl-carnitine could effectively distinguish CHD and DCM patients, and hydroxytetradecanoyl-carnitine and aspartic acid were able to classify CHD and VHD cohorts.Conclusion: This study indicated that circulating amino acids and long-chain acylcarnitine levels were closely associated with progression of heart failure. Monitoring these metabolic alterations by LC-MS may help the differentiation of CHD, VHD, and DCM in the early stage, and provide new diagnostics targets or therapeutic interventions.
Highlights
Cardiovascular disease remains to be an enormous clinical and economic burden worldwide
Metabolomics has been widely used in heart failure (HF) mechanistic investigation, and cardiac metabolic impairment is confirmed to be mainly associated with global suppression of metabolic fuel intake [5,6,7,8,9]
Energy production in cardiomyocytes is shifted from fatty acids toward glycosis, anaplerosis, and other forms of metabolism, such as use of lactate, branched-chain amino acids, and ketone bodies [10,11,12], which may not able to compensate for the reduced fatty acid and glucose oxidation and result in energy deficiency and the development of HF
Summary
Cardiovascular disease remains to be an enormous clinical and economic burden worldwide. Coronary heart disease (CHD), dilated cardiomyopathy (DCM) and valvular heart disease (VHD) are the three most common causes of HF. The clinical picture of CHD is defined by an Metabolic Features of Heart Failure atherosclerotic plaque-induced narrowing of the coronary arteries, which results in myocardial ischemia, infarction, and post-infarction HF. DCM may arise as a result of structural and functional myocardial abnormalities that are characterized by systolic dysfunction and dilation of the left and/or right ventricles [2, 3]. Energy production in cardiomyocytes is shifted from fatty acids toward glycosis, anaplerosis, and other forms of metabolism, such as use of lactate, branched-chain amino acids, and ketone bodies [10,11,12], which may not able to compensate for the reduced fatty acid and glucose oxidation and result in energy deficiency and the development of HF
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