Bone morphogenetic protein 6—a possible new player in pathophysiology of heart failure

Banach, Joanna; Gilewski, Wojciech; Słomka, Artur; Buszko, Katarzyna; Błażejewski, Jan; Karasek, Danuta; Rogowicz, Daniel; Żekanowska, Ewa; Sinkiewicz, Wadyslaw

doi:10.1111/1440-1681.12665

Cited by 16 publications

(13 citation statements)

References 15 publications

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“…59 Recent observations of increased BMP6 levels in HF are in concert with these finding, and they suggest a reactive response to cardiac injury. 60 In conclusion, the release of hepcidin and BMP6 during cardiac injury might serve as part of an orchestrated cardiac response to protect the myocardial function. Still, molecular mediators of BMP6 expression in the heart are unknown, whereas the relation of BMP6 with cardiac hepcidin remains to be elucidated.…”

Section: Cardiac Stress Is Regularly Associated With Increased Hepcidmentioning

confidence: 97%

Balance of cardiac and systemic hepcidin and its role in heart physiology and pathology

Vela

2018

Laboratory Investigation

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Hepcidin is the main regulator of iron metabolism in tissues. Its serum levels are mostly correlated with the levels of hepcidin expression from the liver, but local hepcidin can be important for the physiology of other organs as well. There is an increasing evidence that this is the case with cardiac hepcidin. This has been confirmed by studies with models of ischemic heart disease and other heart pathologies. In this review the discussion dissects the role of cardiac hepcidin in cellular homeostasis. This review is complemented with examination of the role of systemic hepcidin in heart disease and its use as a biochemical marker. The relationship between systemic vs local hepcidin in the heart is important because it can help us understand how the fine balance between the actions of two hepcidins affects heart function. Manipulating the axis systemic/cardiac hepcidin could serve as a new therapeutic strategy in heart diseases.

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Section: Cardiac Stress Is Regularly Associated With Increased Hepcidmentioning

confidence: 97%

Balance of cardiac and systemic hepcidin and its role in heart physiology and pathology

Vela

2018

Laboratory Investigation

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“…BMP6 is expressed in developing hearts and mice with combined BMP6 and BMP7 loss exhibit a delay in formation of the outflow tract endocardial cushions (127). Although a clinical study showed increased circulating levels of BMP6 in patients with advanced heart failure (128), information on the regulation and role of BMP6 in the infarcted myocardium is lacking.…”

Section: The Bmp/gdf Subfamilymentioning

confidence: 99%

The Role of the TGF-β Superfamily in Myocardial Infarction

Hanna

Frangogiannis

2019

Front. Cardiovasc. Med.

208

163

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The members of the transforming growth factor β (TGF-β) superfamily are essential regulators of cell differentiation, phenotype and function, and have been implicated in the pathogenesis of many diseases. Myocardial infarction is associated with induction of several members of the superfamily, including TGF-β1, TGF-β2, TGF-β3, bone morphogenetic protein (BMP)-2, BMP-4, BMP-10, growth differentiation factor (GDF)-8, GDF-11 and activin A. This manuscript reviews our current knowledge on the patterns and mechanisms of regulation and activation of TGF-β superfamily members in the infarcted heart, and discusses their cellular actions and downstream signaling mechanisms. In the infarcted heart, TGF-β isoforms modulate cardiomyocyte survival and hypertrophic responses, critically regulate immune cell function, activate fibroblasts, and stimulate a matrix-preserving program. BMP subfamily members have been suggested to exert both pro- and anti-inflammatory actions and may regulate fibrosis. Members of the GDF subfamily may also modulate survival and hypertrophy of cardiomyocytes and regulate inflammation. Important actions of TGF-β superfamily members may be mediated through activation of Smad-dependent or non-Smad pathways. The critical role of TGF-β signaling cascades in cardiac repair, remodeling, fibrosis, and regeneration may suggest attractive therapeutic targets for myocardial infarction patients. However, the pleiotropic, cell-specific, and context-dependent actions of TGF-β superfamily members pose major challenges in therapeutic translation.

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“…BMP2 has been found to alleviate heart failure with type 2 diabetes by inhibiting inflammasome formation ( 27 ), and is inversely correlated with the concentrations of atrial natriuretic peptide and brain natriuretic peptide in chronic heart failure patients with diabetes. Another study observed increased BMP6 in chronic heart failure patients, suggesting that BMP6 may be involved in the pathophysiology of systolic heart failure ( 28 ). In addition, SMAD1 protein was differentially expressed in a high-salt diet-induced HFpEF model ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

Liver-heart cross-talk mediated by coagulation factor XI protects against heart failure

Wang

Zhou

Pan

et al. 2022

Science

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Tissue-tissue communication by endocrine factors is a vital mechanism for physiologic homeostasis. A systems genetics analysis of transcriptomic and functional data from a cohort of diverse, inbred strains of mice predicted that coagulation factor XI (FXI), a liver-derived protein, protects against diastolic dysfunction, a key trait of heart failure with preserved ejection fraction. This was confirmed using gain- and loss-of-function studies, and FXI was found to activate the bone morphogenetic protein (BMP)–SMAD1/5 pathway in the heart. The proteolytic activity of FXI is required for the cleavage and activation of extracellular matrix–associated BMP7 in the heart, thus inhibiting genes involved in inflammation and fibrosis. Our results reveal a protective role of FXI in heart injury that is distinct from its role in coagulation.

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Bone morphogenetic protein 6—a possible new player in pathophysiology of heart failure

Cited by 16 publications

References 15 publications

Balance of cardiac and systemic hepcidin and its role in heart physiology and pathology

Balance of cardiac and systemic hepcidin and its role in heart physiology and pathology

The Role of the TGF-β Superfamily in Myocardial Infarction

Liver-heart cross-talk mediated by coagulation factor XI protects against heart failure

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