TY - JOUR
T1 - Metabolomic profiling of adults with congenital heart disease
AU - Cedars, Ari
AU - Manlhiot, Cedric
AU - Ko, Jong Mi
AU - Bottiglieri, Teodoro
AU - Arning, Erland
AU - Weingarten, Angela
AU - Opotowsky, Alexander
AU - Kutty, Shelby
N1 - Funding Information:
Funding: This project was funded with startup funds from the Baylor Research Institute and the University of Texas Southwestern Medical School.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/8
Y1 - 2021/8
N2 - Metabolomic analysis may provide an integrated assessment in genetically and patho-logically heterogeneous populations. We used metabolomic analysis to gain mechanistic insight into the small and diverse population of adults with congenital heart disease (ACHD). Consecutive ACHD patients seen at a single institution were enrolled. Clinical variables and whole blood were collected at regular clinical visits. Stored plasma samples were analyzed for the concentrations of 674 metabolites and metabolic markers using mass spectrometry with internal standards. These samples were compared to 28 simultaneously assessed healthy non-ACHD controls. Principal com-ponent analysis and multivariable regression modeling were used to identify metabolites associated with clinical outcomes in ACHD. Plasma from ACHD and healthy control patients differed in the concentrations of multiple metabolites. Differences between control and ACHD were greater in number and in degree than those between ACHD anatomic groups. A metabolite cluster containing amino acids and metabolites of amino acids correlated with negative clinical outcomes across all anatomic groups. Metabolites in the arginine metabolic pathway, betaine, dehydroepiandrosterone, cystine, 1-methylhistidine, serotonin and bile acids were associated with specific clinical outcomes. Metabolic markers of disease may both be useful as biomarkers for disease activity and suggest etiologically related pathways as possible targets for disease-modifying intervention.
AB - Metabolomic analysis may provide an integrated assessment in genetically and patho-logically heterogeneous populations. We used metabolomic analysis to gain mechanistic insight into the small and diverse population of adults with congenital heart disease (ACHD). Consecutive ACHD patients seen at a single institution were enrolled. Clinical variables and whole blood were collected at regular clinical visits. Stored plasma samples were analyzed for the concentrations of 674 metabolites and metabolic markers using mass spectrometry with internal standards. These samples were compared to 28 simultaneously assessed healthy non-ACHD controls. Principal com-ponent analysis and multivariable regression modeling were used to identify metabolites associated with clinical outcomes in ACHD. Plasma from ACHD and healthy control patients differed in the concentrations of multiple metabolites. Differences between control and ACHD were greater in number and in degree than those between ACHD anatomic groups. A metabolite cluster containing amino acids and metabolites of amino acids correlated with negative clinical outcomes across all anatomic groups. Metabolites in the arginine metabolic pathway, betaine, dehydroepiandrosterone, cystine, 1-methylhistidine, serotonin and bile acids were associated with specific clinical outcomes. Metabolic markers of disease may both be useful as biomarkers for disease activity and suggest etiologically related pathways as possible targets for disease-modifying intervention.
KW - Adult congenital heart disease
KW - Biomarkers
KW - Metabolomic analysis
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U2 - 10.3390/metabo11080525
DO - 10.3390/metabo11080525
M3 - Article
C2 - 34436466
AN - SCOPUS:85112680350
SN - 2218-1989
VL - 11
JO - Metabolites
JF - Metabolites
IS - 8
M1 - 525
ER -