Aortic valve disease in diabetes: Molecular mechanisms and novel therapies

Manduteanu, Ileana; Simionescu, Dan T.; Simionescu, Anca A.; Simionescu, Maya

doi:10.1111/jcmm.16937

Cited by 8 publications

(6 citation statements)

References 94 publications

(170 reference statements)

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“…Diabetes is a well-established risk factor of MAC, 19 and MAC can limit the dilation and the motion of mitral valve, which may lead to a low risk of severe MR. 13 Similarly, diabetes may also induce molecules calcification in aortic valve, 20 and inflammatory phenotype of valvular endothelial cells, which are associated with calcific aortic valve disease (CAVD). 21 CAVD may limit the dilation of the aortic root, which leads to the low risk of severe AR.…”

Section: Discussionmentioning

confidence: 99%

Prevalence and impact of diabetes in patients with valvular heart disease

Lu,

Lv,

et al. 2024

iScience

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Section: Discussionmentioning

confidence: 99%

Prevalence and impact of diabetes in patients with valvular heart disease

Lu,

Lv,

et al. 2024

iScience

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“…This may bring some influences to the results. Studies have demonstrated that compared to than non-diabetic patients, patients diabetes showed a significantly elevated risk of CAVD, a significantly greater propensity for developing rapidly progressive AS, and a high degree of calcification in diseased aortic valves ( 65 , 66 ). This may explain the differences of diabetes between CAVD and control groups.…”

Section: Discussionmentioning

confidence: 99%

Integrated proteomic and metabolomic profile analyses of cardiac valves revealed molecular mechanisms and targets in calcific aortic valve disease

Wang

et al. 2022

Front. Cardiovasc. Med.

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BackgroundThis study aimed to define changes in the metabolic and protein profiles of patients with calcific aortic valve disease (CAVD).Methods and resultsWe analyzed cardiac valve samples of patients with and without (control) CAVD (n = 24 per group) using untargeted metabolomics and tandem mass tag-based quantitative proteomics. Significantly different metabolites and proteins between the CAVD and control groups were screened; then, functional enrichment was analyzed. We analyzed co-expressed differential metabolites and proteins, and constructed a metabolite-protein-pathway network. The expression of key proteins was validated using western blotting. Differential analysis identified 229 metabolites in CAVD among which, 2-aminophenol, hydroxykynurenine, erythritol, carnosine, and choline were the top five. Proteomic analysis identified 549 differentially expressed proteins in CAVD, most of which were localized in the nuclear, cytoplasmic, extracellular, and plasma membranes. Levels of selenium binding protein 1 (SELENBP1) positively correlated with multiple metabolites. Adenosine triphosphate-binding cassette transporters, starch and sucrose metabolism, hypoxia-inducible factor 1 (HIF-1) signaling, and purine metabolism were key pathways in the network. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), calcium2+/calmodulin-dependent protein kinase II delta (CAMK2D), and ATP binding cassette subfamily a member 8 (ABCA8) were identified as hub proteins in the metabolite-protein-pathway network as they interacted with ADP, glucose 6-phosphate, choline, and other proteins. Western blotting confirmed that ENPP1 was upregulated, whereas ABCA8 and CAMK2D were downregulated in CAVD samples.ConclusionThe metabolic and protein profiles of cardiac valves from patients with CAVD significantly changed. The present findings provide a holistic view of the molecular mechanisms underlying CAVD that may lead to the development of novel diagnostic biomarkers and therapeutic targets to treat CAVD.

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“…Diabetes can decrease the number and induce dysfunction of endothelial progenitor cells, impairing valve endothelial repair ( 30 ). Indeed, diabetes has been shown to be associated with aortic valve and bioprosthetic aortic valve degeneration ( 31 , 32 ). At the molecular level, diabetes can lead to the upregulation of biglycan, which may contribute to aortic valve degeneration ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Diabetes Is Associated With Rapid Progression of Aortic Stenosis: A Single-Center Retrospective Cohort Study

Han

Shi

Yang

et al. 2022

Front. Cardiovasc. Med.

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BackgroundMounting evidence indicates that rapid progression of aortic stenosis (AS) is significantly associated with poor prognosis. Whether diabetes accelerates the progression of AS remains controversial.ObjectivesThe purpose of the present study was to investigate whether diabetes was associated with rapid progression of AS.MethodsWe retrospectively analyzed 276 AS patients who underwent transthoracic echocardiography at least twice with a maximum interval ≥ 180 days from January 2016 to June 2021. AS severity was defined by specific threshold values for peak aortic jet velocity (Vmax) and/or mean pressure gradient. An increase of Vmax ≥ 0.3 m/s/year was defined as rapid progression. The binary Logistic regression models were used to determine the association between diabetes and rapid progression of AS.ResultsAt a median echocardiographic follow-up interval of 614 days, the annual increase of Vmax was 0.16 (0.00–0.41) m/s. Compared with those without rapid progression, patients with rapid progression were older and more likely to have diabetes (P = 0.040 and P = 0.010, respectively). In the univariate binary Logistic regression analysis, diabetes was associated with rapid progression of AS (OR = 2.02, P = 0.011). This association remained significant in the multivariate analysis based on model 2 and model 3 (OR = 1.93, P = 0.018; OR = 1.93, P = 0.022). After propensity score-matching according to Vmax, diabetes was also associated rapid progression of AS (OR = 2.57, P = 0.045).ConclusionsDiabetes was strongly and independently associated with rapid progression of AS.

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Aortic valve disease in diabetes: Molecular mechanisms and novel therapies

Cited by 8 publications

References 94 publications

Prevalence and impact of diabetes in patients with valvular heart disease

Prevalence and impact of diabetes in patients with valvular heart disease

Integrated proteomic and metabolomic profile analyses of cardiac valves revealed molecular mechanisms and targets in calcific aortic valve disease

Diabetes Is Associated With Rapid Progression of Aortic Stenosis: A Single-Center Retrospective Cohort Study

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