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Probing the Role of Metabolomics to Unveil the Molecular Landscape of Cardiovascular Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 January 2025) | Viewed by 9591

Special Issue Editors

Dr. Sílvia O. Diaz

E-Mail Website
Guest Editor
Faculty of Medicine, University of Porto (FMUP), Porto, Portugal
Interests: metabolomics; lipidomics; cardiovascular diseases; biostatistics
Dr. Antonio Barros

E-Mail Website
Guest Editor
Faculty of Medicine, University of Porto (FMUP), Porto, Portugal
Interests: statistical; machine learning

Special Issue Information

Dear Colleagues,

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality. Despite significant advances in medical interventions and treatments, our understanding of the onset, progression, and related comorbidities of CVD remains incomplete. Thus, understanding of the molecular landscape and mechanisms involved in CVD and their interplay with related comorbidities are highly sought. Metabolomics enables the simultaneous measurement of hundreds of metabolites, leveraging the understanding of the molecular basis of CVD phenotypes. Recognising the importance of bridging the knowledge gap in this area, this Special Issue aims to gather research that sheds light on the intricate relationship between metabolisms and cardiovascular diseases.

This Special Issue will be a dedicated collection of relevant reviews or original articles using metabolomics to understand the molecular landscape of CVD and related comorbidities or risk factors, e.g., diabetes, dyslipidemias, obesity, hypertension, lifestyle, or nutrition. The scope encompasses a broad range of topics, including, but not limited to, the following:

  • Metabolic risk factors and their impact on CVDs;
  • Metabolic syndrome and its association with CVDs;
  • Molecular mechanisms linking metabolism to CVD pathogenesis;
  • Novel diagnostic and therapeutic strategies targeting metabolic dysregulation in CVDs;
  • Comorbidities, such as diabetes, obesity, and dyslipidemia, concerning CVDs;
  • Metabolic profiling and biomarker discovery for early detection and prognosis of CVDs;
  • Bioinformatic and network analysis techniques to elucidate the molecular pathways involved in CVDs;
  • Nutritional interventions and lifestyle modifications for prevention and management of CVDs.

By bringing together high-quality research expertise in the field, we aim to provide a comprehensive overview of the latest contribution of metabolomics for the unveiling of the molecular basis of CVD. We cordially invite researchers to submit their work and help showcase the added value of metabolomics in cardiovascular research. We also encourage manuscripts that address crucial technical issues, such as standardisation and harmonisation across various stages of research, including sample handling, data analysis, reporting, and sharing.

Dr. Sílvia O. Diaz
Dr. Antonio Barros
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

 

Keywords

  • cardiovascular disease
  • metabolomics
  • lipidomics
  • metabolic phenotypes
  • systems biology

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Published Papers (4 papers)

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Research

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18 pages, 1640 KiB  
Article
Identification of Urine Metabolic Markers of Stroke Risk Using Untargeted Nuclear Magnetic Resonance Analysis
by Nádia Oliveira, Adriana Sousa, Ana Paula Amaral, Ricardo Conde and Ignacio Verde
Int. J. Mol. Sci. 2024, 25(13), 7436; https://doi.org/10.3390/ijms25137436 - 6 Jul 2024
Cited by 1 | Viewed by 1944
Abstract
Stroke remains the second leading cause of mortality worldwide, and the third leading cause of death and morbidity combined, affecting more than 12 million people every year. Stroke pathophysiology results from complex interactions of several risk factors related to age, family history, gender, [...] Read more.
Stroke remains the second leading cause of mortality worldwide, and the third leading cause of death and morbidity combined, affecting more than 12 million people every year. Stroke pathophysiology results from complex interactions of several risk factors related to age, family history, gender, lifestyle, and the presence of cardiovascular and metabolic diseases. Despite all the evidence, it is not possible to fully prevent stroke onset. In recent years, there has been an exploration of innovative methodologies for metabolite analysis aimed at identifying novel stroke biomarkers. Utilizing Nuclear Magnetic Resonance (NMR) spectroscopy, we investigated small molecule variations in urine across different stages of stroke risk. The Framingham Stroke Risk Score was used in people over 63 years of age living in long-term care facilities (LTCFs) to calculate the probability of suffering a stroke: low stroke risk (LSR, control), moderate stroke risk (MSR), and high stroke risk (HSR). Univariate statistical analysis showed that urinary 4-hydroxyphenylacetate levels increased while glycolate levels decreased across the different stroke risk groups, from the LSR to the HSR groups. Trimethylamine N-oxide (TMAO) had average concentration values that were significantly higher in elderly people in the HSR group, while trigonelline levels were significantly lower in the MSR group. These metabolic markers can be used for early detection and to differentiate stages of stroke risk more efficiently. Full article
(This article belongs to the Special Issue Probing the Role of Metabolomics to Unveil the Molecular Landscape of Cardiovascular Diseases)
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15 pages, 7044 KiB  
Article
Anaerobutyricum soehngenii Reduces Hepatic Lipogenic Pathways and Increases Intestinal Gluconeogenic Gene Expression in Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD) Mice
by Anne Linde Mak, Quinten J. J. Augustijn, Clément J. F. Heymann, Stefan Havik, Xanthe Verdoes, Melany Rios-Morales, Laura A. Bosmans, Joanne Verheij, Abraham S. Meijnikman, Patrick A. de Jonge, Hilde Herrema, Willem M. de Vos, Max Nieuwdorp, Aldo Grefhorst and Adriaan G. Holleboom
Int. J. Mol. Sci. 2024, 25(6), 3481; https://doi.org/10.3390/ijms25063481 - 20 Mar 2024
Cited by 1 | Viewed by 2527
Abstract
Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a growing health problem for which no therapy exists to date. The modulation of the gut microbiome may have treatment potential for MASLD. Here, we investigated Anaerobutyricum soehngenii, a butyrate-producing anaerobic bacterium with beneficial effects in [...] Read more.
Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a growing health problem for which no therapy exists to date. The modulation of the gut microbiome may have treatment potential for MASLD. Here, we investigated Anaerobutyricum soehngenii, a butyrate-producing anaerobic bacterium with beneficial effects in metabolic syndrome, in a diet-induced MASLD mouse model. Male C57BL/6J mice received a Western-type high-fat diet and water with 15% fructose (WDF) to induce MASLD and were gavaged with A. soehngenii (108 or 109 colony-forming units (CFU) 3 times per week) or a placebo for 6 weeks. The A. soehngenii gavage increased the cecal butyrate concentrations. Although there was no effect on histological MASLD scores, A. soehngenii improved the glycemic response to insulin. In the liver, the WDF-associated altered expression of three genes relevant to the MASLD pathophysiology was reversed upon treatment with A. soehngenii: Lipin-1 (Lpin1), insulin-like growth factor binding protein 1 (Igfbp1) and Interleukin 1 Receptor Type 1 (Il1r1). A. soehngenii administration also increased the intestinal expression of gluconeogenesis and fructolysis genes. Although these effects did not translate into significant histological improvements in MASLD, these results provide a basis for combined gut microbial approaches to induce histological improvements in MASLD. Full article
(This article belongs to the Special Issue Probing the Role of Metabolomics to Unveil the Molecular Landscape of Cardiovascular Diseases)
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10 pages, 723 KiB  
Communication
Cardiogenic Shock Integrated PHenotyping for Event Reduction: A Pilot Metabolomics Analysis
by Nuccia Morici, Gianfranco Frigerio, Jonica Campolo, Silvia Fustinoni, Alice Sacco, Laura Garatti, Luca Villanova, Guido Tavazzi, Navin K. Kapur and Federico Pappalardo
Int. J. Mol. Sci. 2023, 24(24), 17607; https://doi.org/10.3390/ijms242417607 - 18 Dec 2023
Cited by 1 | Viewed by 1456
Abstract
Cardiogenic shock (CS) portends a dismal prognosis if hypoperfusion triggers uncontrolled inflammatory and metabolic derangements. We sought to investigate metabolomic profiles and temporal changes in IL6, Ang-2, and markers of glycocalyx perturbation from admission to discharge in eighteen patients with heart failure complicated [...] Read more.
Cardiogenic shock (CS) portends a dismal prognosis if hypoperfusion triggers uncontrolled inflammatory and metabolic derangements. We sought to investigate metabolomic profiles and temporal changes in IL6, Ang-2, and markers of glycocalyx perturbation from admission to discharge in eighteen patients with heart failure complicated by CS (HF-CS). Biological samples were collected from 18 consecutive HF-CS patients at admission (T0), 48 h after admission (T1), and at discharge (T2). ELISA analytical techniques and targeted metabolomics were performed Seven patients (44%) died at in-hospital follow-up. Among the survivors, IL-6 and kynurenine were significantly reduced at discharge compared to baseline. Conversely, the amino acids arginine, threonine, glycine, lysine, and asparagine; the biogenic amine putrescine; multiple sphingolipids; and glycerophospholipids were significantly increased. Patients with HF-CS have a metabolomic fingerprint that might allow for tailored treatment strategies for the patients’ recovery or stabilization. Full article
(This article belongs to the Special Issue Probing the Role of Metabolomics to Unveil the Molecular Landscape of Cardiovascular Diseases)
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Review

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16 pages, 1753 KiB  
Review
Metabolomics and Cardiovascular Risk in Patients with Heart Failure: A Systematic Review and Meta-Analysis
by Leonel Sousa Neves, Francisca Saraiva, Rita Ferreira, Adelino Leite-Moreira, António S. Barros and Sílvia O. Diaz
Int. J. Mol. Sci. 2024, 25(11), 5693; https://doi.org/10.3390/ijms25115693 - 23 May 2024
Viewed by 2871
Abstract
The associations of plasma metabolites with adverse cardiovascular (CV) outcomes are still underexplored and may be useful in CV risk stratification. We performed a systematic review and meta-analysis to establish correlations between blood metabolites and adverse CV outcomes in patients with heart failure [...] Read more.
The associations of plasma metabolites with adverse cardiovascular (CV) outcomes are still underexplored and may be useful in CV risk stratification. We performed a systematic review and meta-analysis to establish correlations between blood metabolites and adverse CV outcomes in patients with heart failure (HF). Four cohorts were included, involving 83 metabolites and 37 metabolite ratios, measured in 1158 HF patients. Hazard ratios (HR) of 42 metabolites and 3 metabolite ratios, present in at least two studies, were combined through meta-analysis. Higher levels of histidine (HR 0.74, 95% CI [0.64; 0.86]) and tryptophan (HR 0.82 [0.71; 0.96]) seemed protective, whereas higher levels of symmetric dimethylarginine (SDMA) (HR 1.58 [1.30; 1.93]), N-methyl-1-histidine (HR 1.56 [1.27; 1.90]), SDMA/arginine (HR 1.38 [1.14; 1.68]), putrescine (HR 1.31 [1.06; 1.61]), methionine sulfoxide (HR 1.26 [1.03; 1.52]), and 5-hydroxylysine (HR 1.25 [1.05; 1.48]) were associated with a higher risk of CV events. Our findings corroborate important associations between metabolic imbalances and a higher risk of CV events in HF patients. However, the lack of standardization and data reporting hampered the comparison of a higher number of studies. In a future clinical scenario, metabolomics will greatly benefit from harmonizing sample handling, data analysis, reporting, and sharing. Full article
(This article belongs to the Special Issue Probing the Role of Metabolomics to Unveil the Molecular Landscape of Cardiovascular Diseases)
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