ArticleInternational journal of molecular sciences2021
Metabolomics in Severe Aortic Stenosis Reveals Intermediates of Nitric Oxide Synthesis as Most Distinctive Markers.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 21 citations in OpenAlex.
- Triglyceride-glucose index, plasma metabolome and aortic stenosis: a Mendelian randomization analysis.Journal of cardiothoracic surgery · 2026Article
- Electrical Remodeling of Pressure Overloaded Rat Heart Is Attenuated if Imposed During Proliferative Cardiac Growth.Acta physiologica (Oxford, England) · 2025Article
- Serum metabolic profiling in rheumatic heart disease and degenerative aortic stenosis.Scientific reports · 2025Article
- Plasma levels of NO-related pathway molecules to predict post-transcatheter aortic valve implantation major adverse cardiovascular events: a prospective, multicenter study.Postepy w kardiologii interwencyjnej = Advances in interventional cardiology · 2025Article
- A three-dimensional valve-on-chip microphysiological system implicates cell cycle progression, cholesterol metabolism and protein homeostasis in early calcific aortic valve disease progression.Acta biomaterialia · 2024Article
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- Metabolic Signatures of Cardiac Dysfunction, Multimorbidity, and Post-Transcatheter Aortic Valve Implantation Death.Journal of the American Heart Association · 2023Article
- High-Throughput Metabolomics Applications in Pathogenesis and Diagnosis of Valvular Heart Disease.Reviews in cardiovascular medicine · 2023Review
- Small molecule metabolites: discovery of biomarkers and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Metabolomic Profiling in Patients with Different Hemodynamic Subtypes of Severe Aortic Valve Stenosis.Biomolecules · 2023Article
- Mechanical injury accentuates lipid deposition in ApoEFrontiers in cardiovascular medicine · 2023Article
- Integrin-Linked Kinase Expression in Human Valve Endothelial Cells Plays a Protective Role in Calcific Aortic Valve Disease.Antioxidants (Basel, Switzerland) · 2022Article
- The Haemodynamic and Pathophysiological Mechanisms of Calcific Aortic Valve Disease.Biomedicines · 2022Review
- Physical Performance and Non-Esterified Fatty Acids in Men and Women after Transcatheter Aortic Valve Implantation (TAVI).Nutrients · 2022Article
- Towards Personalized Therapy of Aortic Stenosis.Journal of personalized medicine · 2021Review
- Tracing triggers of cardiac remodelling and heart failure.Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation · 2021Article
- On the Role of Paraoxonase-1 and Chemokine Ligand 2 (C-C motif) in Metabolic Alterations Linked to Inflammation and Disease. A 2021 Update.Biomolecules · 2021Review
- Diabetes Mellitus and Its Implications in Aortic Stenosis Patients.International journal of molecular sciences · 2021Review
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundCalcific aortic valve disease (CAVD) is a rapidly growing global health problem with an estimated 12.6 million cases globally in 2017 and a 112% increase of deaths since 1990 due to aging and population growth. CAVD may develop into aortic stenosis (AS) by progressive narrowing of the aortic valve. AS is underdiagnosed, and if treatment by aortic valve replacement (AVR) is delayed, this leads to poor recovery of cardiac function, absence of symptomatic improvement and marked increase of mortality. Considering the current limitations to define the stage of AS-induced cardiac remodeling, there is need for a novel method to aid in the diagnosis of AS and timing of intervention, which may be found in metabolomics profiling of patients.
methodsSerum samples of nine healthy controls and 10 AS patients before and after AVR were analyzed by untargeted mass spectrometry. Multivariate modeling was performed to determine a metabolic profile of 30 serum metabolites which distinguishes AS patients from controls. Human cardiac microvascular endothelial cells (CMECs) were incubated with serum of the AS patients and then stained for ICAM-1 with Western Blot to analyze the effect of AS patient serum on endothelial cell activation.
resultsThe top 30 metabolic profile strongly distinguishes AS patients from healthy controls and includes 17 metabolites related to nitric oxide metabolism and 12 metabolites related to inflammation, in line with the known pathomechanism for calcific aortic valve disease. Nine metabolites correlate strongly with left ventricular mass, of which three show reversal back to control values after AVR. Western blot analysis of CMECs incubated with AS patient sera shows a significant reduction (14%) in ICAM-1 in AS samples taken after AVR compared to AS patient sera before AVR.
conclusionOur study defined a top 30 metabolic profile with biological and clinical relevance, which may be used as blood biomarker to identify AS patients in need of cardiac surgery. Future studies are warranted in patients with mild-to-moderate AS to determine if these metabolites reflect disease severity and can be used to identify AS patients in need of cardiac surgery.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.