Piezo1 and BKCa channels in human atrial fibroblasts: Interplay and remodelling in atrial fibrillation

Jakob, Dorothee; Klesen, Alexander; Allegrini, Benoit; Darkow, Elisa; Aria, Diana; Emig, Ramona; Chica, Ana Simon; Rog-Zielinska, Eva A; Guth, Tim; Beyersdorf, Friedhelm; Kari, Fabian A.; Proksch, Susanne; Hatem, Stéphane; Kretzler, Matthias; Künzel, Stephan; Guizouarn, Hélène; Schmidt, Constanze; Kohl, Peter; Ravens, Ursula; Peyronnet, Rémi

doi:10.1016/j.yjmcc.2021.05.002

Cited by 41 publications

(30 citation statements)

References 58 publications

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“…Reference source not found. ), as reported before [63]. Only a small number of HAFprim displayed TREK-1 activity.…”

Section: Trek-1 Is Present But Lowly Expressed In Hafprim and Implica...supporting

confidence: 81%

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TREK-1 knock-down in human atrial fibroblasts leads to a myofibroblastic phenotype: a role in phenoconversion and over-view of mechano-sensitive channel mRNA expression in cardiac diseases

Darkow

Yusuf

Rajamani

et al. 2022

Preprint

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Cardiac cell mechanical environment changes on a beat-by-beat basis and also in the course of various cardiac diseases. Cells sense and adapt to such mechanical cues via specialized mecha-no-sensors mediating adaptive signaling cascades. Here, we report TREK-1 mRNA expression and activity in human atrial fibroblasts and reveal a cross talk between TREK-1 and fibroblast phenoconversion. With the aim to reveal additional candidates underlying mechano-transduction relevant to cardiac diseases, we investigated mechano-sensitive ion channels (MSC) mRNA ex-pression in diseased and non-diseased human hearts. Our results showed higher TREK-1 expression and activity in fibroblasts compared to myo-fibroblasts and we found that TREK-1 down-regulation leads a more myofibroblastic phenotype suggesting a role for this mechano-sensor in phenoconversion. In addition, TREK-1 is preferen-tially expressed in the left atrium compared to the right one and its expression is not significantly changed when fibroblasts from patients in sinus rhythm vs. sustained atrial fibrillation are com-pared. At the whole-heart level, numerous MSC were differentially expressed between atrial and ventricular or between non-diseased and diseased tissue samples. Thus, we identify atrial fibroblast-specific TREK-1 expression and activity and reveal a role of TREK-1 in atrial fibroblast pheno-conversion. We also provide a comprehensive overview of cardiac MSC mRNA expression in atrial and ventricular tissue from diseased and non-diseased patients, identifying potential novel candidates underlying mechanotransduction in cardiac diseases.

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“…Reference source not found. ), as reported before [63]. Only a small number of HAFprim displayed TREK-1 activity.…”

Section: Trek-1 Is Present But Lowly Expressed In Hafprim and Implica...supporting

confidence: 81%

“…HAF prim were isolated using the outgrowth method as described earlier [63]. Conceptually, fibroblasts grow out of myocardial chunks placed into culture medium due to their migratory and proliferative potential.…”

Section: Methodsmentioning

confidence: 99%

TREK-1 knock-down in human atrial fibroblasts leads to a myofibroblastic phenotype: a role in phenoconversion and over-view of mechano-sensitive channel mRNA expression in cardiac diseases

Darkow

Yusuf

Rajamani

et al. 2022

Preprint

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“…In one report [ 130 ], Piezo1 dysfunctional regulation was investigated within atrial fibrillation. It was observed that in non-passaged right atrial fibroblasts from atrial fibrillation (AF), patients’ Piezo1 expression and activity were higher compared to those patients in sinus rhythm (SR).…”

Section: Piezo1 and The Heartmentioning

confidence: 99%

“…It was observed that in non-passaged right atrial fibroblasts from atrial fibrillation (AF), patients’ Piezo1 expression and activity were higher compared to those patients in sinus rhythm (SR). However, when passaged fibroblasts were analyzed, it was observed that SR cells become more “AF-like” with the absence of a significant difference in Piezo1 between the two conditions [ 130 ]. This important achievement highlights the fibroblasts Piezo1 role in this kind of supraventricular arrhythmia.…”

Section: Piezo1 and The Heartmentioning

confidence: 99%

Piezo1 Channel as a Potential Target for Hindering Cardiac Fibrotic Remodeling

Braidotti

Chen

Long³

et al. 2022

IJMS

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Fibrotic tissues share many common features with neoplasms where there is an increased stiffness of the extracellular matrix (ECM). In this review, we present recent discoveries related to the role of the mechanosensitive ion channel Piezo1 in several diseases, especially in regulating tumor progression, and how this can be compared with cardiac mechanobiology. Based on recent findings, Piezo1 could be upregulated in cardiac fibroblasts as a consequence of the mechanical stress and pro-inflammatory stimuli that occurs after myocardial injury, and its increased activity could be responsible for a positive feedback loop that leads to fibrosis progression. The increased Piezo1-mediated calcium flow may play an important role in cytoskeleton reorganization since it induces actin stress fibers formation, a well-known characteristic of fibroblast transdifferentiation into the activated myofibroblast. Moreover, Piezo1 activity stimulates ECM and cytokines production, which in turn promotes the phenoconversion of adjacent fibroblasts into new myofibroblasts, enhancing the invasive character. Thus, by assuming the Piezo1 involvement in the activation of intrinsic fibroblasts, recruitment of new myofibroblasts, and uncontrolled excessive ECM production, a new approach to blocking the fibrotic progression can be predicted. Therefore, targeted therapies against Piezo1 could also be beneficial for cardiac fibrosis.

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“…Stretch-activated ion channels have been proposed as mechanical sensors and transducers in the heart [ 5 , 6 ], and recent attention has been given to PIEZO1 calcium (Ca 2+ )-permeable, nonselective cation channels, which are activated by mechanical forces, such as membrane stretch and fluid flow [ 7 , 8 , 9 , 10 , 11 , 12 ]. PIEZO1 channels are expressed in cardiac fibroblasts, where they respond to membrane stretch and matrix stiffness, signalling to important downstream mediators, such as interleukin-6 (IL-6), p38 mitogen-activated protein kinase (MAPK), brain natriuretic peptide (BNP), tenascin C (TNC) and transforming growth factor β1 gene expression [ 13 , 14 , 15 , 16 ]. Mechanical stretch has been linked to the triggering of inflammatory cascade in the heart, notably through fibroblast activation [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Global PIEZO1 Gain-of-Function Mutation Causes Cardiac Hypertrophy and Fibrosis in Mice

Bartoli

Evans

Blythe

et al. 2022

Cells

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PIEZO1 is a subunit of mechanically-activated, nonselective cation channels. Gain-of-function PIEZO1 mutations are associated with dehydrated hereditary stomatocytosis (DHS), a type of anaemia, due to abnormal red blood cell function. Here, we hypothesised additional effects on the heart. Consistent with this hypothesis, mice engineered to contain the M2241R mutation in PIEZO1 to mimic a DHS mutation had increased cardiac mass and interventricular septum thickness at 8–12 weeks of age, without altered cardiac contractility. Myocyte size was greater and there was increased expression of genes associated with cardiac hypertrophy (Anp, Acta1 and β-MHC). There was also cardiac fibrosis, increased expression of Col3a1 (a gene associated with fibrosis) and increased responses of isolated cardiac fibroblasts to PIEZO1 agonism. The data suggest detrimental effects of excess PIEZO1 activity on the heart, mediated in part by amplified PIEZO1 function in cardiac fibroblasts.

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Piezo1 and BKCa channels in human atrial fibroblasts: Interplay and remodelling in atrial fibrillation

Cited by 41 publications

References 58 publications

TREK-1 knock-down in human atrial fibroblasts leads to a myofibroblastic phenotype: a role in phenoconversion and over-view of mechano-sensitive channel mRNA expression in cardiac diseases

TREK-1 knock-down in human atrial fibroblasts leads to a myofibroblastic phenotype: a role in phenoconversion and over-view of mechano-sensitive channel mRNA expression in cardiac diseases

Piezo1 Channel as a Potential Target for Hindering Cardiac Fibrotic Remodeling

Global PIEZO1 Gain-of-Function Mutation Causes Cardiac Hypertrophy and Fibrosis in Mice

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