Metabolomics in Pulmonary Hypertension—A Useful Tool to Provide Insights into the Dark Side of a Tricky Pathology
Abstract
:1. Introduction
2. Materials and Methods
2.1. Search Strategy
2.2. Study Selection
2.3. Data Extraction
3. Results
3.1. Pulmonary Hypertension
3.1.1. PH Pathogenesis
3.1.2. Specific PH Subtypes
3.1.3. New Pathogenetic Mechanisms
3.1.4. Right Ventricular Function
3.2. Pulmonary Arterial Hypertension
3.2.1. PAH Pathogenesis
3.2.2. Specific PAH Subtypes
3.2.3. New Pathogenetic Mechanisms
3.2.4. Right Ventricular Function
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Group | Metabolomic Fingerprint |
---|---|
Group 1 | Reduced concentrations of omega-3 polyunsaturated fatty acids and increased concentrations of omega-6 metabolites (persistent pulmonary hypertension of the newborn) Changes in arginine, pyrimidine, purine, and tryptophan metabolic pathways (pulmonary hypertension induced by drugs) Disturbances involving fatty acid metabolism, reactive oxygen species, and the extracellular matrix (pulmonary hypertension induced by pulmonary vein stenosis) |
Group 2 | Overexpression of long-chain acylcarnitines, acetylcarnitine, and monounsaturated fatty acids (pulmonary hypertension induced by heart failure) |
Group 3 | Alterations of the levels of lactate, glutamate, and adenosine 5′-triphosphate (pulmonary hypertension induced by congenital diaphragmatic hernia) Unbalanced lactate and pyruvate levels (pulmonary hypertension induced by chronic obstructive pulmonary disease) Increased malondialdehyde concentrations, reduced glutathione peroxidase and superoxide dismutase activities, changes in purine, arginine, and proline metabolic pathways (pulmonary hypertension induced by chronic exposure to high altitude) |
Group 4 | Glycolysis-derived metabolites, ketone bodies, tricarboxilic acid cycle intermediates (energy imbalance); sphingolipids and lysophospholipids (cellular signaling); rise in fatty acids, glycerol, acyl carnitines, beta-hydroxybutyrate, amino sugars and modified amino acids, and nucleosides levels, decrease in acylcholines and lysophospholipids levels (increase in lipolysis, fatty acid oxidation, and ketogenesis) (pulmonary hypertension induced by chronic thromboembolism) |
Group 5 | No studies have been carried out on this group |
Group | Metabolomic Fingerprint |
---|---|
Group 1 | Alterations in fatty acid synthesis, drops in the levels of sugars, amino sugars, and nucleotide sugars intermediates of protein and lipid glycosylation, and reduced expression of crucial compounds belonging to glutathione and nicotinamide adenine dinucleotide (NAD) metabolism were detected (idiopathic pulmonary arterial hypertension) Changes in spermine metabolism, raised activation of myo-inositol oxidase and the fatty acid pathway, reduced pyruvate production (idiopathic pulmonary arterial hypertension) Disruption in the urea cycle (idiopathic pulmonary arterial hypertension) Changes in the levels of lysophosphatidylcholine, phosphatidylcholine, perillic acid, palmitoleic acid, N-acetylcholine-d-sphingomyelin, oleic acid, palmitic acid, and 2-octenoylcarnitine metabolites (idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension induced by congenital heart disease) Raised levels of serotonin, taurine, creatine, sarcosine, and 2-oxobutanoate and decreased levels of vanillylmandelic acid, 3,4-dihydroxymandelate, 15-keto-prostaglandin F2α, fructose 6-phosphate, l-glutamine, dehydroascorbate, hydroxypyruvate, threonine, l-cystine, and 1-aminocyclopropane-1-carboxylate; changes in purine, glycerophospholipid, galactose, and pyrimidine metabolism; alterations in alanine, glucose, glycine, threonine, and lactate levels; alterations in S-adenosyl methionine and guanine metabolism (pulmonary arterial hypertension induced by congenital heart disease) Raised concentrations of fatty acid metabolites (including lignoceric acid and nervonic acid), eicosanoids/oxylipins, and sex hormone metabolites (pulmonary arterial hypertension induced by connective tissue disease). Disarrangements in lipidic metabolism, glycolysis, energy metabolism, ketogenesis, and methionine metabolism; disrupted iron homeostasis, glutathione metabolism, and lipid peroxidation related to ferroptosis; disruption in the urea cycle (adenosine monophosphate, urea, 4-hydroxy-proline, ornithine, N-acetylornithine); increased di-methylation level of H3K36; increased glycolytic dependence and glutaminolysis induction, reduced fatty acid metabolism; aspartate and glutathione upregulation, phosphate, α-ketoglutarate, inositol, glutamine, 5-oxoproline, hexose phosphate, creatine, pantothenic acid and acetylcarnitine down regulation (alterations in the processes of glycolysis, fatty acid metabolism, oxidative phosphorylation, and tricarboxylic acid cycle); increased levels of glycogen synthase kinase-3β and sterol regulatory element-binding protein 1 and reduced levels of hexokinase 2 and carnitine palmitoyltransferase I (pulmonary arterial hypertension induced by drugs) Rise in acetate, alanine, lactate, and lipoprotein levels and drop in gamma-aminobutyrate, arginine, betaine, choline, creatine, creatinine, glucose, glutamate, glutamine, glycine, histidine, phenylalanine, and tyrosine levels (pulmonary arterial hypertension induced by connective tissue diseases) |
Group 2 to 5 | There are no metabolomic studies on these groups |
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Bassareo, P.P.; D’Alto, M. Metabolomics in Pulmonary Hypertension—A Useful Tool to Provide Insights into the Dark Side of a Tricky Pathology. Int. J. Mol. Sci. 2023, 24, 13227. https://doi.org/10.3390/ijms241713227
Bassareo PP, D’Alto M. Metabolomics in Pulmonary Hypertension—A Useful Tool to Provide Insights into the Dark Side of a Tricky Pathology. International Journal of Molecular Sciences. 2023; 24(17):13227. https://doi.org/10.3390/ijms241713227
Chicago/Turabian StyleBassareo, Pier Paolo, and Michele D’Alto. 2023. "Metabolomics in Pulmonary Hypertension—A Useful Tool to Provide Insights into the Dark Side of a Tricky Pathology" International Journal of Molecular Sciences 24, no. 17: 13227. https://doi.org/10.3390/ijms241713227