Metabolomics reveals metabolite changes of patients with pulmonary arterial hypertension in China

The specific mechanism of pulmonary arterial hypertension (PAH) remains elusive. The present study aimed to explore the underlying mechanism of PAH through the identity of novel biomarkers for PAH using metabolomics approach. Serum samples from 40 patients with idiopathic PAH (IPAH), 20 patients with congenital heart disease‐associated PAH (CHD‐PAH) and 20 healthy controls were collected and analysed by ultra‐high‐performance liquid chromatography coupled with high‐resolution mass spectrometry (UPLC‐HRMS). Orthogonal partial least square‐discriminate analysis (OPLS‐DA) was applied to screen potential biomarkers. These results were validated in monocrotaline (MCT)‐induced PAH rat model. The OPLS‐DA model was successful in screening distinct metabolite signatures which distinguished IPAH and CHD‐PAH patients from healthy controls, respectively (26 and 15 metabolites). Unbiased analysis from OPLS‐DA identified 31 metabolites from PAH patients which were differentially regulated compared to the healthy controls. Our analysis showed dysregulation of the different metabolic pathways, including lipid metabolism, glucose metabolism, amino acid metabolism and phospholipid metabolism pathways in PAH patients compared to their healthy counterpart. Among these metabolites from dysregulated metabolic pathways, a panel of metabolites from lipid metabolism and fatty acid oxidation (lysophosphatidylcholine, phosphatidylcholine, perillic acid, palmitoleic acid, N‐acetylcholine‐d‐sphingomyelin, oleic acid, palmitic acid and 2‐Octenoylcarnitine metabolites) were found to have a close association with PAH. The results from the analysis of both real‐time quantitative PCR and Western blot showed that expression of LDHA, CD36, FASN, PDK1 GLUT1 and CPT‐1 in right heart/lung were significantly up‐regulated in MCT group than the control group.

• Publication year

  2020

• Venue

  Journal of Cellular and Molecular Medicine

• Publication date

  2020-01-16

• Fields of study

  Medicine, Chemistry, Environmental Science

• Identifiers
  DOI 10.1111/jcmm.14937PMID 31945804PMCID 7028857
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Metabolomics reveals metabolite changes of patients with pulmonary arterial hypertension in China

  2020cited by this paper
• Plasma Metabolomics Implicates Modified Transfer RNAs and Altered Bioenergetics in the Outcomes of Pulmonary Arterial Hypertension

  2017cited by this paper
• Combined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet

  2017cited by this paper
• Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells

  2017cited by this paper
• TPPU enhanced exercise‐induced epoxyeicosatrienoic acid concentrations to exert cardioprotection in mice after myocardial infarction

  2017cited by this paper
• Guía ESC/ERS 2015 sobre diagnóstico y tratamiento de la hipertensión pulmonar

  2016cited by this paper
• Fatty Acid Metabolic Defects and Right Ventricular Lipotoxicity in Human Pulmonary Arterial Hypertension

  2016cited by this paper
• 2015 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension.

  2016cited by this paper
• Metabolic Profiling of Right Ventricular-Pulmonary Vascular Function Reveals Circulating Biomarkers of Pulmonary Hypertension.

  2016cited by this paper
• Elevated serum HMGB1 in pulmonary arterial hypertension secondary to congenital heart disease.

  2016cited by this paper
• Mechanisms of Lipid Accumulation in the Bone Morphogenetic Protein Receptor Type 2 Mutant Right Ventricle.

  2016cited by this paper
• Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed Rat Lung

  2016cited by this paper
• Inhibition of glucose-transporter 1 (GLUT-1) expression reversed Warburg effect in gastric cancer cell MKN45.

  2015cited by this paper
• Five-Year outcomes of patients enrolled in the REVEAL Registry.

  2015cited by this paper
• Identification of a biochemical marker for endothelial dysfunction using Raman spectroscopy.

  2015cited by this paper
• Fatty Acid Metabolism in Pulmonary Arterial Hypertension: Role in Right Ventricular Dysfunction and Hypertrophy

  2015cited by this paper
• HIF-1-mediated suppression of acyl-CoA dehydrogenases and fatty acid oxidation is critical for cancer progression.

  2014cited by this paper
• Metabolomic Heterogeneity of Pulmonary Arterial Hypertension

  2014cited by this paper
• The Metabolic Theory of Pulmonary Arterial Hypertension

  2014cited by this paper
• The metabolic basis of pulmonary arterial hypertension.

  2014cited by this paper
• L-Carnitine Preserves Endothelial Function in a Lamb Model of Increased Pulmonary Blood Flow

  2013cited by this paper
• Metabolomics in cerebrospinal fluid of patients with amyotrophic lateral sclerosis: an untargeted approach via high-resolution mass spectrometry.

  2013cited by this paper
• Cardiac glutaminolysis: a maladaptive cancer metabolism pathway in the right ventricle in pulmonary hypertension

  2013cited by this paper
• Current trends and challenges in sample preparation for global metabolomics using liquid chromatography–mass spectrometry

  2012cited by this paper
• Lung ¹⁸F-fluorodeoxyglucose positron emission tomography for diagnosis and monitoring of pulmonary arterial hypertension.

  2012cited by this paper
• Metabolic dysfunction in the pathogenesis of pulmonary hypertension.

  2010cited by this paper
• Protective role of the antidiabetic drug metformin against chronic experimental pulmonary hypertension

  2009cited by this paper
• Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation

  2009cited by this paper
• PDK-1 regulates lactate production in hypoxia and is associated with poor prognosis in head and neck squamous cancer

  2008cited by this paper
• Altered carnitine homeostasis is associated with decreased mitochondrial function and altered nitric oxide signaling in lambs with pulmonary hypertension.

  2008cited by this paper
• AMPK-mediated increase in myocardial long-chain fatty acid uptake critically depends on sarcolemmal CD36.

  2007cited by this paper
• Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance.

  2006cited by this paper
• Increased [18F]fluorodeoxyglucose accumulation in right ventricular free wall in patients with pulmonary hypertension and the effect of epoprostenol.

  2005cited by this paper
• 5‐hydroxytryptamine and the pulmonary circulation: receptors, transporters and relevance to pulmonary arterial hypertension

  2000cited by this paper
• Controlling the false discovery rate: a practical and powerful approach to multiple testing

  1995cited by this paper

• Metabolic Reprogramming Mechanisms and Precision Medicine Strategies for Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

  2026cites this paper
• The Emerging Role of Lactate and Lactylation Modifications in the Pathophysiology of Atherosclerotic Cardiovascular Diseases.

  2025cites this paper
• Lactate Metabolism and Lactylation Modification: New Opportunities and Challenges in Cardiovascular Disease

  2025cites this paper
• Energy metabolism in cardiovascular diseases: unlocking the hidden powerhouse of cardiac pathophysiology

  2025cites this paper
• Physiologic relevance of the transpulmonary metabolome in connective tissue disease–associated pulmonary vascular disease

  2025cites this paper
• Dysfunction in mitochondrial electron transport chain drives the pathogenesis of pulmonary arterial hypertension: insights from a multi-omics investigation

  2025cites this paper
• Decoding PAH-Associated Myopathy: Omics-Based Insights into Myopathy and Exercise Intolerance.

  2025cites this paper
• Exploring the interplay between mitochondria and endoplasmic reticulum in pulmonary arterial hypertension

  2025cites this paper
• TSH promotes right ventricle hypertrophy and energy metabolism remodeling in PAH mice

  2025cites this paper
• Mitochondrial arginase 2 regulates hematopoietic and cardiovascular adaptation to hypoxia

  2025cites this paper
• Phospholysine phosphohistidine inorganic pyrophosphate phosphatase Suppresses Glycolysis and Proliferation of Pulmonary Artery Smooth Muscle Cells in Hypoxic Pulmonary Hypertension via Inhibition of lactate dehydrogenase A.

  2025cites this paper
• Plasma Lipidomic Alterations in Fontan Circulation Reflect Cardiovascular Functional Reserve

  2025cites this paper
• Comprehensive proteomic characterization of pulmonary arterial hypertension in Chinese people

  2025cites this paper
• Identification of plasma lipid metabolism and potential biomarkers in patients with different coronary occlusive acute myocardial infarction

  2025cites this paper
• Rhodiola crenulata extract inhibits cell pyroptosis to ameliorate pulmonary vascular remodeling in rats through the regulation of decadienylcarnitine/NLRP3/GSDMD axis.

  2025cites this paper
• Metabolic Alterations Associated With Right Ventricular Dysfunction in Pulmonary Arterial Hypertension: The Modulatory Effects and Improvement Mechanisms of Exercise

  2025cites this paper
• Role of inflammation in endothelial responses in Pulmonary Hypertension.

  2025cites this paper
• Mitochondrial cardiovascular diseases: molecular mechanisms, multi-omics exploration and therapeutic strategies.

  2025cites this paper
• A metabolic profiling study of pulmonary arterial hypertension

  2024cites this paper
• Decoding the Knacks of Ellagitannin Lead Compounds to Treat Nonalcoholic Fatty Liver Disease using Computer-aided Drug Designing

  2024cites this paper
• Right ventricular dysfunction in preclinical models of type I and type II diabetes.

  2024cites this paper
• A multimodal approach identifies lactate as a central feature of right ventricular failure that is detectable in human plasma

  2024cites this paper
• Metabolomic study on the effect of Indonesian propolis in hypertensive rats

  2024cites this paper
• Serum-based metabolomics reveals the mechanism of action of isorhynchophylline in the intervention of atherosclerosis in ApoE-/- mice.

  2024cites this paper
• Functions and novel regulatory mechanisms of key glycolytic enzymes in pulmonary arterial hypertension.

  2024cites this paper
• Understanding pulmonary hypertension: the need for an integrative metabolomics and transcriptomics approach.

  2024cites this paper
• Unveiling the metabolic landscape of pulmonary hypertension: insights from metabolomics

  2024cites this paper
• Pulmonary Hypertension and Hyperglycemia—Not a Sweet Combination

  2024cites this paper
• Mechanisms of cordycepin in the treatment of pulmonary arterial hypertension in rats based on metabonomics and transcriptomics

  2024cites this paper
• Role of Exercise in Pulmonary Hypertension: Evidence from Bench to Bedside

  2024cites this paper
• Lipocalin‐2 induced LDHA expression promotes vascular remodelling in pulmonary hypertension

  2024cites this paper
• Circulating biomarkers in pulmonary arterial hypertension: State-of-the-art review and future directions

  2024cites this paper
• Identification of fatty acid metabolism signature genes in patients with pulmonary arterial hypertension using WGCNA and machine learning

  2024cites this paper
• Exercise improves systemic metabolism in a monocrotaline model of pulmonary hypertension

  2024cites this paper
• Identification of metabolic biomarkers in idiopathic pulmonary arterial hypertension using targeted metabolomics and bioinformatics analysis

  2024cites this paper
• MiR-21-3p inhibitor exerts myocardial protective effects by altering macrophage polarization state and reducing excessive mitophagy

  2024cites this paper
• Investigating the causal relationship between human blood metabolites and pulmonary hypertension: a two-sample Mendelian randomization study

  2024cites this paper
• Blood L‐cystine levels positively related to increased risk of hypertension

  2024cites this paper
• Metabolic characterization of neurogenetic disorders involving glutamatergic neurotransmission

  2023cites this paper
• The impact of hypertension for metabolites in patients with acute coronary syndrome

  2023cites this paper
• Association of plasma acylcarnitines and amino acids with hypertension: A nationwide metabolomics study

  2023cites this paper
• Transpulmonary amino acid metabolism in the sugen hypoxia model of pulmonary hypertension

  2023cites this paper
• Targeting Mitochondrial Metabolic Dysfunction in Pulmonary Hypertension: Toward New Therapeutic Approaches?

  2023cites this paper
• Current understanding of the contribution of lactate to the cardiovascular system and its therapeutic relevance

  2023cites this paper
• Plasma Lipidomics Analysis Reveals the Potential Role of Lysophosphatidylcholines in Abdominal Aortic Aneurysm Progression and Formation

  2023cites this paper
• Deriving Convergent and Divergent Metabolomic Correlates of Pulmonary Arterial Hypertension

  2023cites this paper
• Comparative Metabolomics in Single Ventricle Patients after Fontan Palliation: A Strong Case for a Targeted Metabolic Therapy

  2023cites this paper
• Changes in Choline Metabolites and Ceramides in Response to a DASH-Style Diet in Older Adults

  2023cites this paper
• Metabolomics in Pulmonary Hypertension—A Useful Tool to Provide Insights into the Dark Side of a Tricky Pathology

  2023cites this paper
• Type 2 diabetes mellitus increases postoperative recurrence risk in Chinese patients with chronic rhinosinusitis

  2023cites this paper
• Metabolomics Meets Clinics: A Multivariate Analysis of Plasma and Urine Metabolic Signatures in Pulmonary Arterial Hypertension

  2023cites this paper
• Serum Metabolomic Profile in Hypoxia-Induced Pulmonary Hypertension Mice after C75 Treatment.

  2023influential citation
• Omics analysis of the effect of cold normal saline stress through gastric gavage on LPS induced mice

  2023cites this paper
• Novel Relationship between Mitofusin 2-Mediated Mitochondrial Hyperfusion, Metabolic Remodeling, and Glycolysis in Pulmonary Arterial Endothelial Cells

  2023cites this paper
• RNA methylation, metabolic reprogramming and pulmonary hypertension

  2023cites this paper
• Altered Lung Microbiome and Metabolome Profile in Children With Pulmonary Arterial Hypertension Associated With Congenital Heart Disease

  2022cites this paper
• Development of a multiomics model for identification of predictive biomarkers for COVID-19 severity: a retrospective cohort study

  2022cites this paper
• A systematic review with meta-analysis of biomarkers for detection of pulmonary arterial hypertension

  2022cites this paper
• Metabolomics-based mechanism exploration of pulmonary arterial hypertension pathogenesis: novel lessons from explanted human lungs

  2022cites this paper
• Integrated metabolomics and mechanism to reveal the protective effect of kaempferol on pulmonary arterial hypertension.

  2022cites this paper
• Mitochondrial Metabolism, Redox, and Calcium Homeostasis in Pulmonary Arterial Hypertension

  2022cites this paper
• Fatty Acid Metabolism in Endothelial Cell

  2022influential citation
• Metabolomics: A New Tool in Our Understanding of Congenital Heart Disease

  2022cites this paper
• NMR-Based Metabolomic Analysis of Plasma in Patients with Adult Congenital Heart Disease and Associated Pulmonary Arterial Hypertension: A Pilot Study

  2022cites this paper
• Changes in Phospholipid/Ceramide Profiles and Eicosanoid Levels in the Plasma of Rats Irradiated with UV Rays and Treated Topically with Cannabidiol

  2021cites this paper
• Role of metabolomics in identifying cardiac hypertrophy: an overview of the past 20 years of development and future perspective

  2021cites this paper
• Identification of Novel Biomarkers for Evaluating Disease Severity in House-Dust-Mite-Induced Allergic Rhinitis by Serum Metabolomics

  2021cites this paper
• Metabolism in Pulmonary Hypertension.

  2021cites this paper
• Effects of sevoflurane anesthesia and abdominal surgery on the systemic metabolome: a prospective observational study

  2021cites this paper
• Sera and lungs metabonomics reveals key metabolites of resveratrol protecting against PAH in rats.

  2021cites this paper
• LDHA mediated degradation of extracellular matrix is a potential target for the treatment of aortic dissection.

  2021cites this paper
• Metabolic Reprogramming of the Right Ventricle and Pulmonary Arteries in a Flow-Associated Pulmonary Arterial Hypertension Rat Model

  2021cites this paper
• Toxicity of Pb continuous and pulse exposure on intestinal anatomy, bacterial diversity, and metabolites of Pelophylax nigromaculatus in pre-hibernation.

  2021cites this paper
• Metabolomics Based Mechanism Exploration of Pulmonary Arterial Hypertension pathogenesis: Novel Lessons from Explanted Lungs

  2021cites this paper
• Targeting Molecular and Cellular Mechanisms in Pulmonary Hypertension

  2021cites this paper
• Potential Cellular Targets Associated with the Signaling of the Pulmonary Hypertension

  2021cites this paper
• Identification of novel metabolic signatures potentially involved in the pathogenesis of COPD associated pulmonary hypertension

  2021cites this paper
• Image diagnosis: Eisenmenger’s syndrome in patients with simple congenital heart disease

  2020cites this paper
• Serum Metabolomic Signatures Associated with Disease Severity in Allergic Rhinitis

  2020cites this paper
• Novel metabolomic profile of subjects with non-classic apparent mineralocorticoid excess

  2020cites this paper
• An Updated Review of Pro- and Anti-Inflammatory Properties of Plasma Lysophosphatidylcholines in the Vascular System

  2020cites this paper
• Novel Molecular Mechanisms of Pulmonary Hypertension: A Search for Biomarkers and Novel Drug Targets—From Bench to Bed Site

  2020cites this paper
• Metabolomics reveals metabolite changes of patients with pulmonary arterial hypertension in China

  2020cites this paper