The role of fibroblast - Cardiomyocyte interaction for atrial dysfunction in HFpEF and hypertensive heart disease
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The role of fibroblast - Cardiomyocyte interaction for atrial dysfunction in HFpEF and hypertensive heart disease. / Bode, David; Lindner, Diana; Schwarzl, Michael; Westermann, Dirk; Deissler, Peter; Primessnig, Uwe; Hegemann, Niklas; Blatter, Lothar A; van Linthout, Sophie; Tschöpe, Carsten; Schoenrath, Felix; Soltani, Sajjad; Stamm, Christof; Duesterhoeft, Volker; Rolim, Natale; Wisløff, Ulrik; Knosalla, Christoph; Falk, Volkmar; Pieske, Burkert M; Heinzel, Frank R; Hohendanner, Felix.
In: J MOL CELL CARDIOL, Vol. 131, 06.2019, p. 53-65.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The role of fibroblast - Cardiomyocyte interaction for atrial dysfunction in HFpEF and hypertensive heart disease
AU - Bode, David
AU - Lindner, Diana
AU - Schwarzl, Michael
AU - Westermann, Dirk
AU - Deissler, Peter
AU - Primessnig, Uwe
AU - Hegemann, Niklas
AU - Blatter, Lothar A
AU - van Linthout, Sophie
AU - Tschöpe, Carsten
AU - Schoenrath, Felix
AU - Soltani, Sajjad
AU - Stamm, Christof
AU - Duesterhoeft, Volker
AU - Rolim, Natale
AU - Wisløff, Ulrik
AU - Knosalla, Christoph
AU - Falk, Volkmar
AU - Pieske, Burkert M
AU - Heinzel, Frank R
AU - Hohendanner, Felix
N1 - Copyright © 2019 Elsevier Ltd. All rights reserved.
PY - 2019/6
Y1 - 2019/6
N2 - AIMS: Atrial contractile dysfunction is associated with increased mortality in heart failure (HF). We have shown previously that a metabolic syndrome-based model of HFpEF and a model of hypertensive heart disease (HHD) have impaired left atrial (LA) function in vivo (rat). In this study we postulate, that left atrial cardiomyocyte (CM) and cardiac fibroblast (CF) paracrine interaction related to the inositol 1,4,5-trisphosphate signalling cascade is pivotal for the manifestation of atrial mechanical dysfunction in HF and that quantitative atrial remodeling is highly disease-dependent.METHODS AND RESULTS: Differential remodeling was observed in HHD and HFpEF as indicated by an increase of atrial size in vivo (HFpEF), unchanged fibrosis (HHD and HFpEF) and a decrease of CM size (HHD). Baseline contractile performance of rat CM in vitro was enhanced in HFpEF. Upon treatment with conditioned medium from their respective stretched CF (CM-SF), CM (at 21 weeks) of WT showed increased Ca2+ transient (CaT) amplitudes related to the paracrine activity of the inotrope endothelin (ET-1) and inositol 1,4,5-trisphosphate induced Ca2+ release. Concentration of ET-1 was increased in CM-SF and atrial tissue from WT as compared to HHD and HFpEF. In HHD, CM-SF had no relevant effect on CaT kinetics. However, in HFpEF, CM-SF increased diastolic Ca2+ and slowed Ca2+ removal, potentially contributing to an in-vivo decompensation. During disease progression (i.e. at 27 weeks), HFpEF displayed dysfunctional excitation-contraction-coupling (ECC) due to lower sarcoplasmic-reticulum Ca2+ content unrelated to CF-CM interaction or ET-1, but associated with enhanced nuclear [Ca2+]. In human patients, tissue ET-1 was not related to the presence of arterial hypertension or obesity.CONCLUSIONS: Atrial remodeling is a complex entity that is highly disease and stage dependent. The activity of fibrosis related to paracrine interaction (e.g. ET-1) might contribute to in vitro and in vivo atrial dysfunction. However, during later stages of disease, ECC is impaired unrelated to CF.
AB - AIMS: Atrial contractile dysfunction is associated with increased mortality in heart failure (HF). We have shown previously that a metabolic syndrome-based model of HFpEF and a model of hypertensive heart disease (HHD) have impaired left atrial (LA) function in vivo (rat). In this study we postulate, that left atrial cardiomyocyte (CM) and cardiac fibroblast (CF) paracrine interaction related to the inositol 1,4,5-trisphosphate signalling cascade is pivotal for the manifestation of atrial mechanical dysfunction in HF and that quantitative atrial remodeling is highly disease-dependent.METHODS AND RESULTS: Differential remodeling was observed in HHD and HFpEF as indicated by an increase of atrial size in vivo (HFpEF), unchanged fibrosis (HHD and HFpEF) and a decrease of CM size (HHD). Baseline contractile performance of rat CM in vitro was enhanced in HFpEF. Upon treatment with conditioned medium from their respective stretched CF (CM-SF), CM (at 21 weeks) of WT showed increased Ca2+ transient (CaT) amplitudes related to the paracrine activity of the inotrope endothelin (ET-1) and inositol 1,4,5-trisphosphate induced Ca2+ release. Concentration of ET-1 was increased in CM-SF and atrial tissue from WT as compared to HHD and HFpEF. In HHD, CM-SF had no relevant effect on CaT kinetics. However, in HFpEF, CM-SF increased diastolic Ca2+ and slowed Ca2+ removal, potentially contributing to an in-vivo decompensation. During disease progression (i.e. at 27 weeks), HFpEF displayed dysfunctional excitation-contraction-coupling (ECC) due to lower sarcoplasmic-reticulum Ca2+ content unrelated to CF-CM interaction or ET-1, but associated with enhanced nuclear [Ca2+]. In human patients, tissue ET-1 was not related to the presence of arterial hypertension or obesity.CONCLUSIONS: Atrial remodeling is a complex entity that is highly disease and stage dependent. The activity of fibrosis related to paracrine interaction (e.g. ET-1) might contribute to in vitro and in vivo atrial dysfunction. However, during later stages of disease, ECC is impaired unrelated to CF.
KW - Animals
KW - Atrial Fibrillation/metabolism
KW - Atrial Remodeling/physiology
KW - Cell Communication/physiology
KW - Echocardiography
KW - Fibroblasts/cytology
KW - Heart Atria/metabolism
KW - Heart Failure/metabolism
KW - Humans
KW - Hypertension/metabolism
KW - Inositol 1,4,5-Trisphosphate/metabolism
KW - Male
KW - Myocytes, Cardiac/cytology
KW - Rats
U2 - 10.1016/j.yjmcc.2019.04.016
DO - 10.1016/j.yjmcc.2019.04.016
M3 - SCORING: Journal article
C2 - 31005484
VL - 131
SP - 53
EP - 65
JO - J MOL CELL CARDIOL
JF - J MOL CELL CARDIOL
SN - 0022-2828
ER -