Identification of metabolomic profile related to adult Fontan pathophysiology

Background: Metabolic disorders are important pathophysiologies that can cause multiple organ dysfunction and worsen prognosis in Fontan patients. This study aimed to comprehensively evaluate the metabolomic profile of adult Fontan patients and characterize its pathophysiology in relation to 2 contr...

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Autores principales:	Noriko Motoki, Hirohiko Motoki, Masafumi Utsumi, Shoko Yamazaki, Haruka Obinata, Kohta Takei, Satoshi Yasukochi
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Fontan procedure Single ventricle Metabolome TCA cycle Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/5108fbc4b6a84d61af617a4994d7efe8
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spelling	oai:doaj.org-article:5108fbc4b6a84d61af617a4994d7efe82021-11-26T04:35:05ZIdentification of metabolomic profile related to adult Fontan pathophysiology2352-906710.1016/j.ijcha.2021.100921https://doaj.org/article/5108fbc4b6a84d61af617a4994d7efe82021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2352906721002098https://doaj.org/toc/2352-9067Background: Metabolic disorders are important pathophysiologies that can cause multiple organ dysfunction and worsen prognosis in Fontan patients. This study aimed to comprehensively evaluate the metabolomic profile of adult Fontan patients and characterize its pathophysiology in relation to 2 control groups. Methods and Results: We performed metabolomic analysis of 31 plasma samples using capillary electrophoresis time-of-flight mass spectrometry. This observational cross-sectional study compared plasma metabolites of 14 heterogeneous adult Fontan patients with those of control groups, including 9 patients with congenital heart disease after biventricular repair and 8 normal healthy controls. Fontan patients exhibited significant differences in intermediate metabolite concentrations related to glycolysis, the tricarboxylic acid (TCA) cycle, and the urea cycle. The plasma concentrations of lactic acid, 2-oxoglutarate, isocitric acid, malic acid, cis-aconitic acid, arginine, citrulline, and the ratio of ornithine/citrulline showed significantly differences among the groups. Multiple logistic regression analysis with a stepwise selection-elimination method identified 2-oxoglutaric acid (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.05–3.76) and cis-aconitic acid (OR 2.69, 95% CI 1.04–6.99) as independently associated with Fontan patients. After adjustment for the covariates of age and gender, 2-oxoglutaric acid (OR 1.97, 95% CI 0.98–3.93) and cis-aconitic acid (OR 3.88, 95% CI 0.99–15.2) showed remarkable relationships with Fontan patients. Conclusions: The present findings suggest that abnormalities in the TCA cycle and amino acid metabolism are distinguishing features in the pathophysiology of Fontan patients. Future metabolomic studies will assist in developing biomarkers for the early prediction of “silent” Fontan pathophysiologies.Noriko MotokiHirohiko MotokiMasafumi UtsumiShoko YamazakiHaruka ObinataKohta TakeiSatoshi YasukochiElsevierarticleFontan procedureSingle ventricleMetabolomeTCA cycleDiseases of the circulatory (Cardiovascular) systemRC666-701ENInternational Journal of Cardiology: Heart & Vasculature, Vol 37, Iss , Pp 100921- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Fontan procedure Single ventricle Metabolome TCA cycle Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	Fontan procedure Single ventricle Metabolome TCA cycle Diseases of the circulatory (Cardiovascular) system RC666-701 Noriko Motoki Hirohiko Motoki Masafumi Utsumi Shoko Yamazaki Haruka Obinata Kohta Takei Satoshi Yasukochi Identification of metabolomic profile related to adult Fontan pathophysiology
description	Background: Metabolic disorders are important pathophysiologies that can cause multiple organ dysfunction and worsen prognosis in Fontan patients. This study aimed to comprehensively evaluate the metabolomic profile of adult Fontan patients and characterize its pathophysiology in relation to 2 control groups. Methods and Results: We performed metabolomic analysis of 31 plasma samples using capillary electrophoresis time-of-flight mass spectrometry. This observational cross-sectional study compared plasma metabolites of 14 heterogeneous adult Fontan patients with those of control groups, including 9 patients with congenital heart disease after biventricular repair and 8 normal healthy controls. Fontan patients exhibited significant differences in intermediate metabolite concentrations related to glycolysis, the tricarboxylic acid (TCA) cycle, and the urea cycle. The plasma concentrations of lactic acid, 2-oxoglutarate, isocitric acid, malic acid, cis-aconitic acid, arginine, citrulline, and the ratio of ornithine/citrulline showed significantly differences among the groups. Multiple logistic regression analysis with a stepwise selection-elimination method identified 2-oxoglutaric acid (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.05–3.76) and cis-aconitic acid (OR 2.69, 95% CI 1.04–6.99) as independently associated with Fontan patients. After adjustment for the covariates of age and gender, 2-oxoglutaric acid (OR 1.97, 95% CI 0.98–3.93) and cis-aconitic acid (OR 3.88, 95% CI 0.99–15.2) showed remarkable relationships with Fontan patients. Conclusions: The present findings suggest that abnormalities in the TCA cycle and amino acid metabolism are distinguishing features in the pathophysiology of Fontan patients. Future metabolomic studies will assist in developing biomarkers for the early prediction of “silent” Fontan pathophysiologies.
format	article
author	Noriko Motoki Hirohiko Motoki Masafumi Utsumi Shoko Yamazaki Haruka Obinata Kohta Takei Satoshi Yasukochi
author_facet	Noriko Motoki Hirohiko Motoki Masafumi Utsumi Shoko Yamazaki Haruka Obinata Kohta Takei Satoshi Yasukochi
author_sort	Noriko Motoki
title	Identification of metabolomic profile related to adult Fontan pathophysiology
title_short	Identification of metabolomic profile related to adult Fontan pathophysiology
title_full	Identification of metabolomic profile related to adult Fontan pathophysiology
title_fullStr	Identification of metabolomic profile related to adult Fontan pathophysiology
title_full_unstemmed	Identification of metabolomic profile related to adult Fontan pathophysiology
title_sort	identification of metabolomic profile related to adult fontan pathophysiology
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/5108fbc4b6a84d61af617a4994d7efe8
work_keys_str_mv	AT norikomotoki identificationofmetabolomicprofilerelatedtoadultfontanpathophysiology AT hirohikomotoki identificationofmetabolomicprofilerelatedtoadultfontanpathophysiology AT masafumiutsumi identificationofmetabolomicprofilerelatedtoadultfontanpathophysiology AT shokoyamazaki identificationofmetabolomicprofilerelatedtoadultfontanpathophysiology AT harukaobinata identificationofmetabolomicprofilerelatedtoadultfontanpathophysiology AT kohtatakei identificationofmetabolomicprofilerelatedtoadultfontanpathophysiology AT satoshiyasukochi identificationofmetabolomicprofilerelatedtoadultfontanpathophysiology
_version_	1718409840908304384

Identification of metabolomic profile related to adult Fontan pathophysiology

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