FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4384568122> ?p ?o ?g. }

• W4384568122 abstract "<h3>Background</h3> We have previously published large-scale cardiac proteomic data from heart failure (HF) patients with ischaemic heart disease (IHD) (Circulation, 2021). No similar proteomics analyses are available on hearts from HF patients with dilated cardiomyopathy (DCM). <h3>Purpose</h3> To compare the effect of comorbidities, medications, and genetic mutations on the cardiac proteome of DCM patients. <h3>Methods</h3> Using quantitative, multiplexed proteomics, we analyzed left ventricular samples from patients with IHD (n=65) and DCM (n=114), and non-failing controls (n=19). Genomic data were obtained by whole-exome sequencing. <h3>Results</h3> In all HF patients, a reduction in myofilament-related proteins was accompanied by a marked increase in cardiac tissue concentrations of atrial natriuretic factor (ANF). Compared to patients with IHD, hearts from DCM patients showed higher levels of proteasome components. In contrast to patients with IHD, few protein changes were associated with medication in DCM patients. Instead, comorbidities such as hypertension and atrial fibrillation were key determinants of the cardiac proteome in DCM. Using principal component analysis, we identified 4 clusters of DCM patients: the main clinical characteristics defining each cluster were hypertension, atrial fibrillation, sex and body mass index. With regards to genetic predisposition, almost 1 out of 5 DCM patients were carriers of titin-truncating variants. DCM patients with titin-truncating variants were significantly enriched in two clusters and characterized by a downregulation of thick filament constituents compared to non-carriers. Finally, among all quantified proteins, ANF levels varied the most between DCM patients. Cardiac tissue levels of ANF were highly correlated to the fibroblast activation marker periostin and to extracellular matrix proteoglycans, in particular versican. In contrast, ANF levels did not correlate to the cardiac collagen content. In cultured mouse fibroblasts, ANF stimulation induced proteoglycan expression, suggesting that ANF secreted by cardiomyocytes exerts paracrine effects on neighboring fibroblasts. <h3>Conclusion</h3> In this largest proteomics analysis of human HF to date, we discerned the effects of mutations, medications and comorbidities on the cardiac proteome. DCM-causing mutations are associated with distinct proteomics profiles even in explanted hearts. Moreover, we describe a novel paracrine effect of ANF on the synthesis of proteoglycans by cardiac fibroblasts. Thus, besides its well-known natriuretic effects, ANF may alter the cardiac extracellular matrix composition in DCM patients. This new insight could also advance our mechanistic understanding of the beneficial effects of neprilysin inhibitors in HF, which reduce the break-down of ANF. <h3>Conflict of Interest</h3> n/a" @default.
• W4384568122 created "2023-07-18" @default.
• W4384568122 creator A5000721255 @default.
• W4384568122 creator A5005148667 @default.
• W4384568122 creator A5020567566 @default.
• W4384568122 creator A5026597514 @default.
• W4384568122 creator A5026657861 @default.
• W4384568122 creator A5029587581 @default.
• W4384568122 creator A5031494933 @default.
• W4384568122 creator A5033551109 @default.
• W4384568122 creator A5052540422 @default.
• W4384568122 creator A5073434822 @default.
• W4384568122 creator A5074040210 @default.
• W4384568122 creator A5079419262 @default.
• W4384568122 creator A5086692319 @default.
• W4384568122 creator A5087807880 @default.
• W4384568122 date "2023-06-01" @default.
• W4384568122 modified "2023-10-18" @default.
• W4384568122 title "BS3 Proteomics of human heart failure: effects of mutations, medications and comorbidities" @default.
• W4384568122 doi "https://doi.org/10.1136/heartjnl-2023-bcs.217" @default.
• W4384568122 hasPublicationYear "2023" @default.
• W4384568122 type Work @default.
• W4384568122 citedByCount "0" @default.
• W4384568122 crossrefType "proceedings-article" @default.
• W4384568122 hasAuthorship W4384568122A5000721255 @default.
• W4384568122 hasAuthorship W4384568122A5005148667 @default.
• W4384568122 hasAuthorship W4384568122A5020567566 @default.
• W4384568122 hasAuthorship W4384568122A5026597514 @default.
• W4384568122 hasAuthorship W4384568122A5026657861 @default.
• W4384568122 hasAuthorship W4384568122A5029587581 @default.
• W4384568122 hasAuthorship W4384568122A5031494933 @default.
• W4384568122 hasAuthorship W4384568122A5033551109 @default.
• W4384568122 hasAuthorship W4384568122A5052540422 @default.
• W4384568122 hasAuthorship W4384568122A5073434822 @default.
• W4384568122 hasAuthorship W4384568122A5074040210 @default.
• W4384568122 hasAuthorship W4384568122A5079419262 @default.
• W4384568122 hasAuthorship W4384568122A5086692319 @default.
• W4384568122 hasAuthorship W4384568122A5087807880 @default.
• W4384568122 hasBestOaLocation W43845681221 @default.
• W4384568122 hasConcept C104317684 @default.
• W4384568122 hasConcept C104397665 @default.
• W4384568122 hasConcept C126322002 @default.
• W4384568122 hasConcept C164705383 @default.
• W4384568122 hasConcept C207200792 @default.
• W4384568122 hasConcept C2776383484 @default.
• W4384568122 hasConcept C2778198053 @default.
• W4384568122 hasConcept C2778797674 @default.
• W4384568122 hasConcept C2779161974 @default.
• W4384568122 hasConcept C46111723 @default.
• W4384568122 hasConcept C54355233 @default.
• W4384568122 hasConcept C60644358 @default.
• W4384568122 hasConcept C68731436 @default.
• W4384568122 hasConcept C71924100 @default.
• W4384568122 hasConcept C86803240 @default.
• W4384568122 hasConcept C90671521 @default.
• W4384568122 hasConceptScore W4384568122C104317684 @default.
• W4384568122 hasConceptScore W4384568122C104397665 @default.
• W4384568122 hasConceptScore W4384568122C126322002 @default.
• W4384568122 hasConceptScore W4384568122C164705383 @default.
• W4384568122 hasConceptScore W4384568122C207200792 @default.
• W4384568122 hasConceptScore W4384568122C2776383484 @default.
• W4384568122 hasConceptScore W4384568122C2778198053 @default.
• W4384568122 hasConceptScore W4384568122C2778797674 @default.
• W4384568122 hasConceptScore W4384568122C2779161974 @default.
• W4384568122 hasConceptScore W4384568122C46111723 @default.
• W4384568122 hasConceptScore W4384568122C54355233 @default.
• W4384568122 hasConceptScore W4384568122C60644358 @default.
• W4384568122 hasConceptScore W4384568122C68731436 @default.
• W4384568122 hasConceptScore W4384568122C71924100 @default.
• W4384568122 hasConceptScore W4384568122C86803240 @default.
• W4384568122 hasConceptScore W4384568122C90671521 @default.
• W4384568122 hasLocation W43845681221 @default.
• W4384568122 hasOpenAccess W4384568122 @default.
• W4384568122 hasPrimaryLocation W43845681221 @default.
• W4384568122 hasRelatedWork W2044490050 @default.
• W4384568122 hasRelatedWork W2067977631 @default.
• W4384568122 hasRelatedWork W2073453392 @default.
• W4384568122 hasRelatedWork W2167036398 @default.
• W4384568122 hasRelatedWork W2348720246 @default.
• W4384568122 hasRelatedWork W2742831078 @default.
• W4384568122 hasRelatedWork W2917172139 @default.
• W4384568122 hasRelatedWork W3035006171 @default.
• W4384568122 hasRelatedWork W4379744808 @default.
• W4384568122 hasRelatedWork W1703255818 @default.
• W4384568122 isParatext "false" @default.
• W4384568122 isRetracted "false" @default.
• W4384568122 workType "article" @default.