Circulating Biomarkers of Myocardial Fibrosis

López, Begoña; González, Arantxa; Ravassa, Susana; Beaumont, Javier; Moreno, María U.; José, Gorka San; Querejeta, Ramón; Díez, Javier

doi:10.1016/j.jacc.2015.04.026

Cited by 220 publications

(246 citation statements)

References 46 publications

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“…Recent observations suggest that markers of collagen metabolism, such as N-terminal propeptide of procollagen type III (PIIINP) or C-terminal propeptide of procollagen type I (PICP), are likely better biomarkers of myocardial fibrosis, and circulating levels of these proteins have been validated against histopathologic analysis of fibrosis on EMB. 22 However, these markers were not tested in the present study.…”

Section: Discussionmentioning

confidence: 88%

“…1,21 However, noninvasive monitoring of cardiac fibrosis remains a major challenge in the clinical setting. Although histological assessment of EMBs, as performed in the present study, is considered as the most accurate method to quantify cardiac fibrosis, 22 all patients who undergo EMB are at small but existing risk of complications. With the advent of new imaging modalities, such as cardiac magnetic resonance imaging, postcontrast T1 mapping, and estimation of the extracellular volume fraction, a noninvasive alternative has emerged.…”

Section: Discussionmentioning

confidence: 95%

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Plasma and Cardiac Galectin-3 in Patients With Heart Failure Reflects Both Inflammation and Fibrosis

Besler

Lang

Urban

et al. 2017

Circ: Heart Failure

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Background— Galectin (Gal)-3 is a β-galactoside-binding lectin and currently intensely studied as a biomarker in heart failure. Gal-3 also exerts proinflammatory effects, at least in extracardiac tissues. Objective of this study was to characterize the relationship of plasma and myocardial Gal-3 levels with cardiac fibrosis and inflammation in patients with nonischemic dilated cardiomyopathy and inflammatory cardiomyopathy (iCMP). Methods and Results— Endomyocardial biopsies and blood samples were obtained from patients with newly diagnosed cardiomyopathy and clinical suspicion of myocarditis. According to histopathologic findings, patients were classified as having dilated cardiomyopathy (n=40) or iCMP (n=75). Cardiac fibrosis was assessed histologically on endomyocardial biopsy sections. In patients with iCMP, myocardial Gal-3 expression significantly correlated with inflammatory cell count on endomyocardial biopsy ( r =0.56; P <0.05). In contrast, an inverse association was observed between myocardial Gal-3 expression and cardiac fibrosis in patients with iCMP ( r =−0.59; P <0.05). In patients with dilated cardiomyopathy, myocardial Gal-3 expression correlated with cardiac fibrosis on left ventricular biopsy ( P =0.63; P <0.01). Of note, in both groups, plasma Gal-3 levels did not correlate with myocardial Gal-3 levels or left ventricular fibrosis, whereas a positive correlation between plasma Gal-3 levels and inflammatory cell count on endomyocardial biopsy was observed in patients with iCMP. Conclusions— The present study suggests that myocardial Gal-3 can be considered as a possible marker for both cardiac inflammation and fibrosis, depending on the pathogenesis of heart failure. However, circulating concentrations of Gal-3 do not seem to reflect endomyocardial Gal-3 levels or cardiac fibrosis.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 95%

Plasma and Cardiac Galectin-3 in Patients With Heart Failure Reflects Both Inflammation and Fibrosis

Besler

Lang

Urban

et al. 2017

Circ: Heart Failure

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“…Presently available evidence in regard to this issue is inconclusive. 46 This may be due, at least in part, to problems associated with the reliable determination of TGF-β 1 plasma levels. 43,44 If these difficulties can be overcome and if methodologies are conceived which permit investigations of electrotonic interactions between myofibroblasts and cardiomyocytes in vivo, plasma levels of TGF-β 1 may eventually turn into a meaningful biomarker for hearts at risk for arrhythmias.…”

Section: Relevance For the Intact Heartmentioning

confidence: 99%

TGF-β ₁ (Transforming Growth Factor-β ₁ ) Plays a Pivotal Role in Cardiac Myofibroblast Arrhythmogenicity

Salvarani

Maguy

Simone

et al. 2017

Circ: Arrhythmia and Electrophysiology

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Background-TGF-β 1 (transforming growth factor-β 1 ) importantly contributes to cardiac fibrosis by controlling differentiation, migration, and collagen secretion of cardiac myofibroblasts. It is still elusive, however, to which extent TGF-β 1 alters the electrophysiological phenotype of myofibroblasts and cardiomyocytes and whether it affects proarrhythmic myofibroblast-cardiomyocyte crosstalk observed in vitro. Methods and Results-Patch-clamp recordings of cultured neonatal rat ventricular myofibroblasts revealed that TGF-β 1 , applied for 24 to 48 hours at clinically relevant concentrations (≤2.5 ng/mL), causes substantial membrane depolarization concomitant with a several-fold increase of transmembrane currents. Transcriptome analysis revealed TGF-β 1 -dependent changes in 29 of 63 ion channel/pump/connexin transcripts, indicating a pleiotropic effect on the electrical phenotype of myofibroblasts. Whereas not affecting cardiomyocyte membrane potentials and cardiomyocyte-cardiomyocyte gap junctional coupling, TGF-β 1 depolarized cardiomyocytes coupled to myofibroblasts by ≈20 mV and increased gap junctional coupling between myofibroblasts and cardiomyocytes >5-fold as reflected by elevated connexin 43 and consortin transcripts. TGF-β 1 -dependent cardiomyocyte depolarization resulted from electrotonic crosstalk with myofibroblasts as demonstrated by immediate normalization of cardiomyocyte electrophysiology after targeted disruption of coupled myofibroblasts and by cessation of ectopic activity of cardiomyocytes coupled to myofibroblasts during pharmacological gap junctional uncoupling. In cardiac fibrosis models exhibiting slow conduction and ectopic activity, block of TGF-β 1 signaling completely abolished both arrhythmogenic conditions. Conclusions-TGF-β 1 profoundly alters the electrophysiological phenotype of cardiac myofibroblasts. Apart from possibly contributing to the control of cell function in general, the changes proved to be pivotal for proarrhythmic myofibroblastcardiomyocyte crosstalk in vitro, which suggests that TGF-β 1 may play a potentially important role in arrhythmogenesis of the fibrotic heart. (Circ Arrhythm Electrophysiol. 2017;10:e004567.

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“…PICP and N‐terminal propeptide of procollagen type III)16 and quality markers (e.g. CITP : MMP‐1) 16…”

Section: Discussionmentioning

confidence: 99%

Rationale of the FIBROTARGETS study designed to identify novel biomarkers of myocardial fibrosis

et al. 2017

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AimsMyocardial fibrosis alters the cardiac architecture favouring the development of cardiac dysfunction, including arrhythmias and heart failure. Reducing myocardial fibrosis may improve outcomes through the targeted diagnosis and treatment of emerging fibrotic pathways. The European‐Commission‐funded ‘FIBROTARGETS’ is a multinational academic and industrial consortium with the main aims of (i) characterizing novel key mechanistic pathways involved in the metabolism of fibrillary collagen that may serve as biotargets, (ii) evaluating the potential anti‐fibrotic properties of novel or repurposed molecules interfering with the newly identified biotargets, and (iii) characterizing bioprofiles based on distinct mechanistic phenotypes involving the aforementioned biotargets. These pathways will be explored by performing a systematic and collaborative search for mechanisms and targets of myocardial fibrosis. These mechanisms will then be translated into individualized diagnostic tools and specific therapeutic pharmacological options for heart failure.Methods and resultsThe FIBROTARGETS consortium has merged data from 12 patient cohorts in a common database available to individual consortium partners. The database consists of >12 000 patients with a large spectrum of cardiovascular clinical phenotypes. It integrates community‐based population cohorts, cardiovascular risk cohorts, and heart failure cohorts.ConclusionsThe FIBROTARGETS biomarker programme is aimed at exploring fibrotic pathways allowing the bioprofiling of patients into specific ‘fibrotic’ phenotypes and identifying new therapeutic targets that will potentially enable the development of novel and tailored anti‐fibrotic therapies for heart failure.

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Circulating Biomarkers of Myocardial Fibrosis

Cited by 220 publications

References 46 publications

Plasma and Cardiac Galectin-3 in Patients With Heart Failure Reflects Both Inflammation and Fibrosis

Plasma and Cardiac Galectin-3 in Patients With Heart Failure Reflects Both Inflammation and Fibrosis

TGF-β ₁ (Transforming Growth Factor-β ₁ ) Plays a Pivotal Role in Cardiac Myofibroblast Arrhythmogenicity

Rationale of the FIBROTARGETS study designed to identify novel biomarkers of myocardial fibrosis

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Circulating Biomarkers of Myocardial Fibrosis

Cited by 220 publications

References 46 publications

Plasma and Cardiac Galectin-3 in Patients With Heart Failure Reflects Both Inflammation and Fibrosis

Plasma and Cardiac Galectin-3 in Patients With Heart Failure Reflects Both Inflammation and Fibrosis

TGF-β 1 (Transforming Growth Factor-β 1 ) Plays a Pivotal Role in Cardiac Myofibroblast Arrhythmogenicity

Rationale of the FIBROTARGETS study designed to identify novel biomarkers of myocardial fibrosis

Contact Info

Product

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TGF-β ₁ (Transforming Growth Factor-β ₁ ) Plays a Pivotal Role in Cardiac Myofibroblast Arrhythmogenicity