CARDIOKIN1: Computational Assessment of Myocardial Metabolic Capability in Healthy Controls and Patients With Valve Diseases.
energy metabolism
heart valve diseases
mathematical model
metabolism
proteomics
Journal
Circulation
ISSN: 1524-4539
Titre abrégé: Circulation
Pays: United States
ID NLM: 0147763
Informations de publication
Date de publication:
14 12 2021
14 12 2021
Historique:
pubmed:
12
11
2021
medline:
8
1
2022
entrez:
11
11
2021
Statut:
ppublish
Résumé
Many heart diseases can result in reduced pumping capacity of the heart muscle. A mismatch between ATP demand and ATP production of cardiomyocytes is one of the possible causes. Assessment of the relation between myocardial ATP production (MV We developed a comprehensive kinetic model of cardiac energy metabolism (CARDIOKIN1) that recapitulates numerous experimental findings on cardiac metabolism obtained with isolated cardiomyocytes, perfused animal hearts, and in vivo studies with humans. We used the model to assess the energy status of the left ventricle of healthy participants and patients with aortic stenosis and mitral valve insufficiency. Maximal enzyme activities were individually scaled by means of protein abundances in left ventricle tissue samples. The energy status of the left ventricle was quantified by the ATP consumption at rest (MV Compared with controls, in both groups of patients, MV Our analysis suggests that the ATP-producing capacity of the left ventricle of patients with valvular dysfunction is generally diminished and correlates positively with mechanical energy demand and cardiac output. However, large differences exist in the energetic state of the myocardium even in patients with similar clinical or image-based markers of hypertrophy and pump function. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03172338 and NCT04068740.
Sections du résumé
BACKGROUND
Many heart diseases can result in reduced pumping capacity of the heart muscle. A mismatch between ATP demand and ATP production of cardiomyocytes is one of the possible causes. Assessment of the relation between myocardial ATP production (MV
METHOD
We developed a comprehensive kinetic model of cardiac energy metabolism (CARDIOKIN1) that recapitulates numerous experimental findings on cardiac metabolism obtained with isolated cardiomyocytes, perfused animal hearts, and in vivo studies with humans. We used the model to assess the energy status of the left ventricle of healthy participants and patients with aortic stenosis and mitral valve insufficiency. Maximal enzyme activities were individually scaled by means of protein abundances in left ventricle tissue samples. The energy status of the left ventricle was quantified by the ATP consumption at rest (MV
RESULTS
Compared with controls, in both groups of patients, MV
CONCLUSIONS
Our analysis suggests that the ATP-producing capacity of the left ventricle of patients with valvular dysfunction is generally diminished and correlates positively with mechanical energy demand and cardiac output. However, large differences exist in the energetic state of the myocardium even in patients with similar clinical or image-based markers of hypertrophy and pump function. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03172338 and NCT04068740.
Identifiants
pubmed: 34762513
doi: 10.1161/CIRCULATIONAHA.121.055646
pmc: PMC8663543
doi:
Substances chimiques
Adenosine Triphosphate
8L70Q75FXE
Banques de données
ClinicalTrials.gov
['NCT03172338', 'NCT04068740']
Types de publication
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1926-1939Références
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