Searching for new mechanisms of myocardial fibrosis with diagnostic and/or therapeutic potential

Heymans, Stéphane; González, Arantxa; Pizard, Anne; Papageorgiou, Anna-Pia; López‐Andrés, Natalia; Jaisser, Frédéric; Thum, Thomas; Zannad, Faı̈ez; Díez, Javier

doi:10.1002/ejhf.312

Cited by 118 publications

(94 citation statements)

References 69 publications

(112 reference statements)

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“…The cardiac extracellular matrix is predominantly composed of fibrillar collagen type I (85%) and type III (11%) 29. Myocardial fibrosis occurs when synthesis of fibrillary collagen types I and III predominates over unchanges or decreased degradation 32. An excess of highly cross‐linked thick collagen type I fibres to the detriment of poorly cross‐linked thin collagen type III fibres is typical of adverse fibrosis 32.…”

Section: Discussionmentioning

confidence: 99%

“…Myocardial fibrosis occurs when synthesis of fibrillary collagen types I and III predominates over unchanges or decreased degradation 32. An excess of highly cross‐linked thick collagen type I fibres to the detriment of poorly cross‐linked thin collagen type III fibres is typical of adverse fibrosis 32. On the other hand, type IV collagens are relatively specifically observed in the liver and partially observed in the basement membrane of the myocytes, in the perivascular, and in the pericellular space in the heart 29.…”

Section: Discussionmentioning

confidence: 99%

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Liver fibrosis score predicts mortality in heart failure patients with preserved ejection fraction

et al. 2017

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AimsHeart failure with preserved ejection fraction (HFpEF) has several pathophysiological aspects, including stiffness and/or congestion of multiple organs. Poor prognosis is expected in heart failure patients with liver stiffness, which has recently been assessed by non‐alcoholic fatty liver disease fibrosis score (NFS; based on aspartate aminotransferase to alanine aminotransferase ratio, platelet counts, and albumin). We aimed to investigate the impact of NFS on prognosis of HFpEF patients, with consideration for the peripheral collagen markers such as procollagen type III peptide (PIIIP), type IV collagen 7S, and hyaluronic acid.Methods and resultsWe performed a prospective observational study. Consecutive 492 hospitalized HFpEF patients were divided into four groups based on their NFS: first–fourth quartiles (n = 123). The fourth quartile group had the highest levels of PIIIP, type IV collagen 7S, hyaluronic acid, and B‐type natriuretic peptide (P<0.001 each). In addition, there were significant positive correlations between PIIIP, type IV collagen 7S, hyaluronic acid, B‐type natriuretic peptide, and NFS (P < 0.001 each). In the follow‐up period (mean 1107 days), 93 deaths occurred. All‐cause mortality increased in all four quartiles (8.1%, 12.2%, 23.6%, and 31.7%, P < 0.001). In the multivariable Cox proportional hazard analysis, NFS was an independent predictor of all‐cause mortality in the HFpEF patients.ConclusionsNFS, a novel indicator of liver fibrosis, correlates with circulating systemic markers of fibrosis and congestion and is associated with higher all‐cause mortality in HFpEF patients. NFS can be calculated simply and may be a useful tool to assess liver stiffness and prognosis in HFpEF patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Liver fibrosis score predicts mortality in heart failure patients with preserved ejection fraction

et al. 2017

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“…3 Although this hypothesis has never been tested in detail in human studies, recent clinical studies have investigated the prognostic value of plasma levels of Gal-3 in the community setting, as well as in a variety of patient populations with heart failure. Higher plasma concentrations of Gal-3 were associated with all-cause mortality and risk of heart failure in the general population.…”

Section: Discussionmentioning

confidence: 99%

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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“…Recently, new mediators with therapeutic potential of cardiac fibrosis have been emerging such as cardiotrophin-1, galectin, and miRNAs etc. (Fang et al, 2015; Heymans et al, 2015). Although many anti-fibrotic therapies on cardiac fibrosis seem promising in experimental models, clinical data are limited and mixed.…”

Section: Introductionmentioning

confidence: 99%

A Clinical Perspective of Anti-Fibrotic Therapies for Cardiovascular Disease

2017

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Cardiac fibrosis are central to various cardiovascular diseases. Research on the mechanisms and therapeutic targets for cardiac fibrosis has advanced greatly in recent years. However, while many anti-fibrotic treatments have been studied in animal models and seem promising, translation of experimental findings into human patients has been rather limited. Thus, several potential new treatments which have shown to reduce cardiac fibrosis in animal models have either not been tested in humans or proved to be disappointing in clinical trials. A majority of clinical studies are of small size or have not been maintained for long enough periods. In addition, although some conventional therapies, such as renin-angiotensin-aldosterone system (RAAS) inhibitors, have been shown to reduce cardiac fibrosis in humans, cardiac fibrosis persists in patients with heart failure even when treated with these conventional therapies, indicating a need to develop novel and effective anti-fibrotic therapies in cardiovascular disease. In this review article, we summarize anti-fibrotic therapies for cardiovascular disease in humans, discuss the limitations of currently used therapies, along with possible reasons for the failure of so many anti-fibrotic drugs at the clinical level. We will then explore the future directions of anti-fibrotic therapies on cardiovascular disease, and this will include emerging anti-fibrotics that show promise, such as relaxin. A better understanding of the differences between animal models and human pathology, and improved insight into carefully designed trials on appropriate end-points and appropriate dosing need to be considered to identify more effective anti-fibrotics for treating cardiovascular fibrosis in human patients.

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Searching for new mechanisms of myocardial fibrosis with diagnostic and/or therapeutic potential

Cited by 118 publications

References 69 publications

Liver fibrosis score predicts mortality in heart failure patients with preserved ejection fraction

Liver fibrosis score predicts mortality in heart failure patients with preserved ejection fraction

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

A Clinical Perspective of Anti-Fibrotic Therapies for Cardiovascular Disease

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