Aortic Valve Stenosis and Atrial Fibrillation Influence Plasma Fibulin-1 Levels in Patients Treated with Coronary Bypass Surgery

Hansen, Morten Hartvig; Dahl, Jordi S.; Argraves, W. Scott; Irmukhamedov, Akhmadjon; Rasmussen, Lars Melholt

doi:10.1159/000354217

Cited by 14 publications

(10 citation statements)

References 17 publications

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“…However, no association was shown in the multivariable analyses. This is partly in accordance with data from patients with aorta stenosis, where fibulin-1 levels were related with S’, but not with LVEF [10]. Furthermore, we demonstrated a moderate, inverse association with eGFR which could blunt a potential weaker association with LV contractile reserve.…”

Section: Discussionsupporting

confidence: 92%

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Galectin-3 and fibulin-1 in systolic heart failure - relation to glucose metabolism and left ventricular contractile reserve

Holmager

Egstrup

Gustafsson

et al. 2017

BMC Cardiovasc Disord

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BackgroundHeart failure (HF) patients with diabetes (DM) have an adverse prognosis and reduced functional capacity, which could be associated with cardiac fibrosis, increased chamber stiffness and reduced left ventricular (LV) contractile reserve. Galectin-3 (Gal-3) and fibulin-1 are circulating biomarkers potentially reflecting cardiac fibrosis. We hypothesize that plasma levels of Gal-3 and fibulin-1 are elevated in HF patients with DM and are associated with reduced LV contractile reserve in these patients.MethodsA total of 155 patients with HF with reduced ejection fraction underwent a low-dose dobutamine echocardiography and blood sampling for biomarker measurements. Patients were classified according to history of DM and an oral glucose tolerance test (OGTT) as: normal glucose tolerance (NGT) (n = 70), impaired glucose tolerance (IGT) (n = 25) and DM (n = 60).ResultsGalectin-3 levels were elevated in DM patients as compared to non-diabetic patients (P = 0.02), while higher fibulin-1 levels were observed in HF patients with IGF and DM (P = 0.07). Reduced LV contractile reserve was associated with increasing Gal-3 levels (β = −0.19, P = 0.03) although, this association was attenuated after adjustment for estimated glomerular filtration rate (P = 0.66). Fibulin-1 was not associated with LV contractile reserve (P = 0.71).ConclusionsGalectin-3 and fibulin-1 levels were elevated in HF patients with impaired glucose metabolism. However, reduced LV contractile reserve among HF patients with DM does not to have an independent impact on plasma Gal-3 and fibulin-1 levels.

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Section: Discussionsupporting

confidence: 92%

“…Fibulin-1 is an extracellular matrix glycoprotein and is considered to reflect pathological accumulation of extracellular matrix components surrounding vascular smooth muscle cells [10]. To our knowledge no previous studies of fibulin-1 in HFrEF patients have been performed.…”

Section: Introductionmentioning

confidence: 99%

Galectin-3 and fibulin-1 in systolic heart failure - relation to glucose metabolism and left ventricular contractile reserve

Holmager

Egstrup

Gustafsson

et al. 2017

BMC Cardiovasc Disord

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“…FBLN1 levels are increased in serum and bronchoalveolar lavage fluid of asthma patients (Lau, et al, 2010) and in the plasma and lung tissue of IPF patients (Jaffar, et al, 2014). Based on our results, we observe an association between FBLN1 and fibrotic diseases; this is also corroborated in existing bibliography (Ge, et al, 2015;Hansen, et al, 2013;Jaffar, et al, 2012) regarding specific tissues (e.g., lung, myocardium). We suggest that further proteomics analyses should be performed to measure the quantity of the fibulin-1 translated protein in the related fibrotic tissues and its potential involvement in fibrosis.…”

Section: Discussionsupporting

confidence: 89%

“…Finally, Hansen et al study FBLN1 with regard to myocardial fibrosis. In (Hansen, et al, 2013), they suggest that, since Aortic Valve Stenosis (AVS) causes cardiac fibrosis and since they observe elevated expression of the FBLN1 gene in AVS samples against controls, the FBLN1 must be expressed as part of the fibrotic process. Even though FBLN1 is undeniably implicated in various fibrotic diseases, its expression levels in different tissues and its actual role regarding different fibrotic diseases should be further tested.…”

Section: Key Fibrosis-related Genesmentioning

confidence: 99%

Drug Repurposing Through a Bioinformatics Pipeline Applied on Fibrotic Diseases

Karatzas¹,

Kakouri

Kolios

et al. 2020

Preprint

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AbstractSubjectFibrotic diseases cover a spectrum of systemic and organ-specific maladies that affect a large portion of the population, currently without cure. The shared characteristic these diseases feature is their uncontrollable fibrogenesis deemed responsible for the accumulated damage in the susceptible tissues. Idiopathic Pulmonary Fibrosis (IPF), an interstitial lung disease, is one of the most common and studied fibrotic diseases and still remains an active research target.ObjectiveWe highlight unique and common (i) genes, (ii) biological pathways and (iii) candidate repurposed drugs among nine fibrotic diseases. We bibliographically explore the resulting candidate substances for potential anti-fibrotic mode of action and focus on diseases that appear to be more similar to IPF so as to jointly examine potential treatments.MethodologyWe identify key genes for the 9 fibrotic diseases by analyzing transcriptomics datasets. We construct gene-to-gene networks for each disease and examine these networks to explore functional communities of biological pathways. We also use the most significant genes as input in Drug Repurposing (DR) tools and re-rank the resulting candidates according to their structural properties and functional relationship to each investigated disease.ResultsWe identify 7 biological pathways involved in all 9 fibrotic diseases as well as pathways unique to some of these diseases. Based on our DR results, we suggest captopril and ibuprofen that both appear to slow the progression of fibrotic diseases according to existing bibliography. We also recommend nafcillin and memantine, which haven’t been studied against fibrosis yet, for further wet-lab experimentation. We also observe a group of cardiomyopathy-related pathways that are exclusively highlighted for Oral Submucous Fibrosis (OSF). We suggest digoxin to be tested against OSF, since we observe cardiomyopathy-related pathways implicated in OSF and there is bibliographic evidence that digoxin may potentially clear myocardial fibrosis. Finally, we establish that IPF shares several involved genes, biological pathways and candidate inhibiting-drugs with Dupuytren’s Disease, IgG4-related Disease, SSc and Cystic Fibrosis. We propose that treatments for these fibrotic diseases should be jointly pursued.

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“…Beyond LV hypertrophy development of fibrosis plays a role in myocardial remodeling in AS. Although we can only speculate on the degree of myocardial fibrosis, we have recently shown that fibulin-1 levels were elevated in patients with known AF undergoing cardiac surgery compared to patients with sinus rhythm [19]. Additionally, we have demonstrated that fibulin-1 levels correlated with echocardiographic indices of myocardial stiffness and increased filling pressures suggesting that fibulin-1 might be a marker of myocardial fibrosis.…”

Section: Discussionmentioning

confidence: 83%

Atrial fibrillation in severe aortic valve stenosis — Association with left ventricular left atrial remodeling

Dahl

Brandes

Videbæk

et al. 2014

IJC Heart & Vessels

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Background: Atrial fibrillation (AF) is common in patients with aortic stenosis (AS) although the exact mechanism is unclear. The purpose of this study was to investigate echocardiographic characteristics among patients with severe AS and AF and to identify factors associated with the development of new-onset AF after aortic valve replacement (AVR). Methods: 125 patients with severe AS and ejection fraction N 40% scheduled for AVR were evaluated preoperatively and 3, 6, 9 and 12 months postoperatively with electrocardiography (ECG) and echocardiography, and Holter-ECG analysis was performed after 3 and 12 months. The primary endpoint was new-onset AF defined as an episode of AF exceeding 30 s, on the ECG or Holter-ECG and/or patients hospitalized due to AF. Results: AF was present in 19 patients prior to AVR, compared to patients in sinus rhythm AF patients had increased NT-proBNP, increased left atrial (LA) volume (61 ± 21 vs. 47 ± 17 ml/m 2 , p = 0.002), reduced global longitudinal left ventricular strain (−13.1 ± 3.7 vs. −16.0 ± 3.5, p = 0.002) and presented more often with a restrictive filling pattern (37% vs. 10%, p = 0.002). During follow-up 23 patients developed new-onset AF; predictors were LA volume, restrictive filling pattern, NT-proBNP, E/e′ and systolic blood pressure. After correcting for age and LA volume index, a restrictive filling pattern and systolic blood pressure remained associated with new-onset AF. Conclusions: The presence of preoperative AF and development of new-onset AF after AVR is associated with restrictive filling pattern and LA dilatation in patients with severe AS.

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Aortic Valve Stenosis and Atrial Fibrillation Influence Plasma Fibulin-1 Levels in Patients Treated with Coronary Bypass Surgery

Cited by 14 publications

References 17 publications

Galectin-3 and fibulin-1 in systolic heart failure - relation to glucose metabolism and left ventricular contractile reserve

Galectin-3 and fibulin-1 in systolic heart failure - relation to glucose metabolism and left ventricular contractile reserve

Drug Repurposing Through a Bioinformatics Pipeline Applied on Fibrotic Diseases

Atrial fibrillation in severe aortic valve stenosis — Association with left ventricular left atrial remodeling

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