Metabolomic Profiling of Adults with Congenital Heart Disease
Metabolomic analysis may provide an integrated assessment in genetically and pathologically 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 si...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-08-01
|
Series: | Metabolites |
Subjects: | |
Online Access: | https://www.mdpi.com/2218-1989/11/8/525 |
id |
doaj-5bb7590f1efe4cf2a28ecca5e7bf3159 |
---|---|
record_format |
Article |
spelling |
doaj-5bb7590f1efe4cf2a28ecca5e7bf31592021-08-26T14:03:50ZengMDPI AGMetabolites2218-19892021-08-011152552510.3390/metabo11080525Metabolomic Profiling of Adults with Congenital Heart DiseaseAri Cedars0Cedric Manlhiot1Jong-Mi Ko2Teodoro Bottiglieri3Erland Arning4Angela Weingarten5Alexander Opotowsky6Shelby Kutty7Department of Pediatrics, Johns Hopkins University, Baltimore, MD 21218, USADepartment of Pediatrics, Johns Hopkins University, Baltimore, MD 21218, USADepartment of Pediatrics, Johns Hopkins University, Baltimore, MD 21218, USACenter of Metabolomics, Baylor Scott & White Research Institute, Dallas, TX 75204, USACenter of Metabolomics, Baylor Scott & White Research Institute, Dallas, TX 75204, USADepartment of Medicine, Vanderbilt University, Nashville, TN 37235, USADepartment of Cardiology, Cincinnati Children’s Hospital, Cincinnati, OH 45229, USADepartment of Pediatrics, Johns Hopkins University, Baltimore, MD 21218, USAMetabolomic analysis may provide an integrated assessment in genetically and pathologically 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 component 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.https://www.mdpi.com/2218-1989/11/8/525adult congenital heart diseasemetabolomic analysisbiomarkers |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ari Cedars Cedric Manlhiot Jong-Mi Ko Teodoro Bottiglieri Erland Arning Angela Weingarten Alexander Opotowsky Shelby Kutty |
spellingShingle |
Ari Cedars Cedric Manlhiot Jong-Mi Ko Teodoro Bottiglieri Erland Arning Angela Weingarten Alexander Opotowsky Shelby Kutty Metabolomic Profiling of Adults with Congenital Heart Disease Metabolites adult congenital heart disease metabolomic analysis biomarkers |
author_facet |
Ari Cedars Cedric Manlhiot Jong-Mi Ko Teodoro Bottiglieri Erland Arning Angela Weingarten Alexander Opotowsky Shelby Kutty |
author_sort |
Ari Cedars |
title |
Metabolomic Profiling of Adults with Congenital Heart Disease |
title_short |
Metabolomic Profiling of Adults with Congenital Heart Disease |
title_full |
Metabolomic Profiling of Adults with Congenital Heart Disease |
title_fullStr |
Metabolomic Profiling of Adults with Congenital Heart Disease |
title_full_unstemmed |
Metabolomic Profiling of Adults with Congenital Heart Disease |
title_sort |
metabolomic profiling of adults with congenital heart disease |
publisher |
MDPI AG |
series |
Metabolites |
issn |
2218-1989 |
publishDate |
2021-08-01 |
description |
Metabolomic analysis may provide an integrated assessment in genetically and pathologically 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 component 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. |
topic |
adult congenital heart disease metabolomic analysis biomarkers |
url |
https://www.mdpi.com/2218-1989/11/8/525 |
work_keys_str_mv |
AT aricedars metabolomicprofilingofadultswithcongenitalheartdisease AT cedricmanlhiot metabolomicprofilingofadultswithcongenitalheartdisease AT jongmiko metabolomicprofilingofadultswithcongenitalheartdisease AT teodorobottiglieri metabolomicprofilingofadultswithcongenitalheartdisease AT erlandarning metabolomicprofilingofadultswithcongenitalheartdisease AT angelaweingarten metabolomicprofilingofadultswithcongenitalheartdisease AT alexanderopotowsky metabolomicprofilingofadultswithcongenitalheartdisease AT shelbykutty metabolomicprofilingofadultswithcongenitalheartdisease |
_version_ |
1721191572738932736 |