Insulin-Like Growth Factor I, Insulin-like Growth factor Binding Protein 3, and Atrial Fibrillation in the Elderly

Duron, Emmanuelle; Vidal, Jean‐Sébastien; Funalot, Benoît; Brunel, Nadège; Seux, Marie-Laure; Tréluyer, Jean‐Marc; Epelbaum, Jacques; Bouc, Yves Le; Hanon, Olivier

doi:10.1093/gerona/glt206

Cited by 20 publications

(17 citation statements)

References 46 publications

(48 reference statements)

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“…In vivo human studies have demonstrated that infusion of IGF-1 into human brachial arteries increased blood flow in the forearm by NO-dependent mechanisms (20). Lower circulating IGF-1 levels have been associated with the presence of traditional stroke risk factors, particularly diabetes (4,21) and atrial fibrillation (9). Hence, the effects of IGF-1 levels on cerebrovascular events may be mediated through components of the metabolic syndrome and pathways of atrial fibrillation.…”

Section: Discussionmentioning

confidence: 99%

“…IGF-1 also enhances insulin sensitivity (4) and induces vasodilation (5), thereby, regulating glucose homeostasis, blood pressure and cerebral blood flow (6,7). Additionally, low circulating IGF-1 levels have been associated with increased carotid intima-media thickness (8) and atrial fibrillation (9) in an elderly population. Lower levels of IGF-1 have been found to be associated with the presence of traditional vascular risk factors, particularly obesity (10), insulin resistance and diabetes (4,11).…”

Section: Introductionmentioning

confidence: 99%

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Serum Insulin-Like Growth Factor 1 and the Risk of Ischemic Stroke

Saber

Himali

Beiser

et al. 2017

Stroke

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Background Low insulin-like growth factor 1 (IGF-1) have been associated with increased risk of atherosclerosis and atrial fibrillation in cross-sectional studies. Yet, prospective data linking IGF-1 levels to the development of ischemic stroke remain inconclusive. We examined prospectively the association between serum IGF-1 levels and incident ischemic stroke. Methods We measured serum IGF-1 levels in 757 elderly individuals (mean age 79±5, 62% women), free of prevalent stroke, from the Framingham original cohort participants at the 22nd examination cycle (1990-1994) and were followed up for the development of ischemic stroke. Cox models were used to relate IGF-1 levels to the risk for incident ischemic stroke, adjusted for potential confounders. Results During a mean follow-up of 10.2 years, 99 individuals developed ischemic stroke. After adjustment for age, sex and potential confounders, higher IGF-1 levels were associated with a lower risk of incident ischemic stroke with subjects in the lowest quintile of IGF-1 levels having a 2.3-fold higher risk of incident ischemic stroke (95% CI: 1.09-5.06, p=0.03) as compared to the top quintile. We observed an effect modification by diabetes and waist-hip ratio (WHR) for the association between IGF-1 and ischemic stroke (p<0.1). In subgroup analyses, the effects were restricted to diabetics and those in top WHR quartile, in whom each standard deviation increase in IGF-1 was associated with a 61% (HR: 0.39, 95% CI: 0.20-0.78, p=0.007), and 41% (HR: 0.59, 95% CI: 0.37-0.95, p=0.031) lower risk of incident ischemic stroke, respectively. Conclusions IGF-1 levels were inversely associated with ischemic stroke, especially among persons with insulin resistance.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serum Insulin-Like Growth Factor 1 and the Risk of Ischemic Stroke

Saber

Himali

Beiser

et al. 2017

Stroke

View full text Add to dashboard Cite

show abstract

“…Further mechanisms may explain the association between low IGFBP-3 levels and worse outcomes. Recently, low IGFBP-3 levels were found in patients with (1) atrial fibrillation, (2) low hemoglobin concentrations, and (3) chronic hemiparesis [26][27][28]. Despite a relatively small sample size the association between IGFBP-3 and functional outcome was remarkably robust and outscored known predictors of outcome like age, baseline NIHSS, and DWI lesion volume.…”

mentioning

confidence: 99%

Circulating Insulin-like Growth Factor Binding Protein-3 Predicts One-year Outcome after Ischemic Stroke

Ebinger

Ipsen

Leonards

et al. 2015

Exp Clin Endocrinol Diabetes

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“…Indeed, the TGB-beta 1 pathway is regarded as one of the profibrotic mediator that cause selective atrial fibrosis and promote AF [ 73 ]. Low IGF-I serum levels are independently associated with AF in elderly population [ 74 ] and its antiarrhythmic properties have been shown on a rat model with ventricular arrhythmia [ 75 ]. IGF-I protects against atherosclerosis, counteracts endothelial dysfunction, and prevents smooth muscle cell apoptosis [ 76 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the microRNA signature in left atrium from patients with valvular heart disease reveals their implications in atrial fibrillation

et al. 2018

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BackgroundAmong the potential factors which may contribute to the development and perpetuation of atrial fibrillation, dysregulation of miRNAs has been suggested. Thus in this study, we have quantified the basal expressions of 662 mature human miRNAs in left atrium (LA) from patients undergoing cardiac surgery for valve repair, suffering or not from atrial fibrillation (AF) by using TaqMan® Low Density arrays (v2.0).ResultsAmong the 299 miRNAs expressed in all patients, 42 miRNAs had altered basal expressions in patients with AF. Binding-site predictions with Targetscan (conserved sites among species) indicated that the up- and down-regulated miRNAs controlled respectively 3,310 and 5,868 genes. To identify the most relevant cellular functions under the control of the altered miRNAs, we focused on the 100 most targeted genes of each list and identified 5 functional protein-protein networks among these genes. Up-regulated networks were involved in synchronisation of circadian rythmicity and in the control of the AKT/PKC signaling pathway (i.e., proliferation/adhesion). Down-regulated networks were the IGF-1 pathway and TGF-beta signaling pathway and a network involved in RNA-mediated gene silencing, suggesting for the first time that alteration of miRNAs in AF would also perturbate the whole miRNA machinery. Then we crossed the list of miRNA predicted genes, and the list of mRNAs altered in similar patients suffering from AF and we found that respectively 44.5% and 55% of the up- and down-regulated mRNA are predicted to be conserved targets of the altered miRNAs (at least one binding site in 3’-UTR). As they were involved in the same biological processes mentioned above, these data demonstrated that a great part of the transcriptional defects previously published in LA from AF patients are likely due to defects at the post-transcriptional level and involved the miRNAs.ConclusionsOur stringent analysis permitted us to identify highly targeted protein-protein networks under the control of miRNAs in LA and, among them, to highlight those specifically affected in AF patients with altered miRNA signature. Further studies are now required to determine whether alterations of miRNA levels in AF pathology are causal or represent an adaptation to prevent cardiac electrical and structural remodeling.

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Insulin-Like Growth Factor I, Insulin-like Growth factor Binding Protein 3, and Atrial Fibrillation in the Elderly

Abstract: Low IGF-I and low IGFBP-3 serum levels were independently associated with AF in this elderly population. This result should be confirmed in a longitudinal study to evaluate whether IGF-I and/or IGFBP-3 serum levels are predictive of incident AF.

Cited by 20 publications

References 46 publications

Serum Insulin-Like Growth Factor 1 and the Risk of Ischemic Stroke

Serum Insulin-Like Growth Factor 1 and the Risk of Ischemic Stroke

Circulating Insulin-like Growth Factor Binding Protein-3 Predicts One-year Outcome after Ischemic Stroke

Analysis of the microRNA signature in left atrium from patients with valvular heart disease reveals their implications in atrial fibrillation

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