PMID- 32699940
OWN - NLM
STAT- MEDLINE
DCOM- 20210625
LR  - 20211204
IS  - 1435-1803 (Electronic)
IS  - 0300-8428 (Linking)
VI  - 115
IP  - 5
DP  - 2020 Jul 22
TI  - Fibroblast growth factor 23 decreases PDE4 expression in heart increasing the 
      risk of cardiac arrhythmia; Klotho opposes these effects.
PG  - 51
LID - 10.1007/s00395-020-0810-6 [doi]
AB  - The concentration of fibroblast growth factor 23 (FGF23) rises progressively in 
      renal failure (RF). High FGF23 concentrations have been consistently associated 
      with adverse cardiovascular outcomes or death, in chronic kidney disease (CKD), 
      heart failure or liver cirrhosis. We identified the mechanisms whereby high 
      concentrations of FGF23 can increase the risk of death of cardiovascular origin. 
      We studied the effects of FGF23 and Klotho in adult rat ventricular 
      cardiomyocytes (ARVMs) and on the heart of mice with CKD. We show that FGF23 
      increases the frequency of spontaneous calcium waves (SCWs), a marker of 
      cardiomyocyte arrhythmogenicity, in ARVMs. FGF23 increased sarcoplasmic reticulum 
      Ca(2+) leakage, basal phosphorylation of Ca(2+)-cycling proteins including 
      phospholamban and ryanodine receptor type 2. These effects are secondary to a 
      decrease in phosphodiesterase 4B (PDE4B) in ARVMs and in heart of mice with RF. 
      Soluble Klotho, a circulating form of the FGF23 receptor, prevents FGF23 effects 
      on ARVMs by increasing PDE3A and PDE3B expression. Our results suggest that the 
      combination of high FGF23 and low sKlotho concentrations decreases PDE activity 
      in ARVMs, which favors the occurrence of ventricular arrhythmias and may 
      participate in the high death rate observed in patients with CKD.
FAU - Lindner, Marta
AU  - Lindner M
AD  - INSERM U1151-CNRS UMR8253, Paris, France.
FAU - Mehel, Hind
AU  - Mehel H
AD  - INSERM U1151-CNRS UMR8253, Paris, France.
FAU - David, Amandine
AU  - David A
AD  - INSERM U1151-CNRS UMR8253, Paris, France.
FAU - Leroy, Christine
AU  - Leroy C
AD  - INSERM U1151-CNRS UMR8253, Paris, France.
FAU - Burtin, Martine
AU  - Burtin M
AD  - INSERM U1151-CNRS UMR8253, Paris, France.
FAU - Friedlander, Gerard
AU  - Friedlander G
AD  - INSERM U1151-CNRS UMR8253, Paris, France.
AD  - Universite de Paris Faculte de Medecine, Paris, France.
AD  - Service de Physiologie Explorations Fonctionnelles Hopital Europeen Georges 
      Pompidou, Assistance Publique-Hopitaux de Paris, Paris, France.
FAU - Terzi, Fabiola
AU  - Terzi F
AD  - INSERM U1151-CNRS UMR8253, Paris, France.
FAU - Mika, Delphine
AU  - Mika D
AD  - Universite Paris-Saclay, Inserm U1180, 92296, Chatenay-Malabry, France.
FAU - Fischmeister, Rodolphe
AU  - Fischmeister R
AD  - Universite Paris-Saclay, Inserm U1180, 92296, Chatenay-Malabry, France.
FAU - Prie, Dominique
AU  - Prie D
AUID- ORCID: 0000-0003-3478-9778
AD  - INSERM U1151-CNRS UMR8253, Paris, France. dominique.prie@inserm.fr.
AD  - Universite de Paris Faculte de Medecine, Paris, France. dominique.prie@inserm.fr.
AD  - Service de Physiologie Explorations Fonctionnelles Hopital Necker-Enfants 
      Malades, Assistance Publique-Hopitaux de Paris, Paris, France. 
      dominique.prie@inserm.fr.
LA  - eng
GR  - CERF ANR- 13-BSV1-0002-01/Agence Nationale de la Recherche/International
GR  - EFIKAC ANR-16-CE14-0010/Agence Nationale de la Recherche/International
GR  - ANR- 11-LABX-0051/Laboratory of Excellence GR-Ex/International
GR  - ANR-11-IDEX-0005-02/Laboratory of Excellence GR-Ex/International
GR  - ANR-10-LABX-33/LERMIT/International
GR  - ANR-11-IDEX-0003-01/LERMIT/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200722
PL  - Germany
TA  - Basic Res Cardiol
JT  - Basic research in cardiology
JID - 0360342
RN  - 0 (Fgf23 protein, mouse)
RN  - 0 (Fgf23 protein, rat)
RN  - 62031-54-3 (Fibroblast Growth Factors)
RN  - 7Q7P4S7RRE (Fibroblast Growth Factor-23)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4)
RN  - EC 3.1.4.17 (PDE4B protein, rat)
RN  - EC 3.2.1.31 (Glucuronidase)
RN  - EC 3.2.1.31 (Klotho Proteins)
SB  - IM
MH  - Animals
MH  - Arrhythmias, Cardiac/*etiology/metabolism
MH  - Calcium Signaling
MH  - Cardiomegaly/etiology
MH  - Cyclic AMP/metabolism
MH  - Cyclic Nucleotide Phosphodiesterases, Type 4/*metabolism
MH  - Excitation Contraction Coupling
MH  - Fibroblast Growth Factor-23
MH  - Fibroblast Growth Factors/*metabolism
MH  - Glucuronidase/*metabolism
MH  - Klotho Proteins
MH  - Male
MH  - Mice
MH  - Myocytes, Cardiac/*metabolism
MH  - Nephrectomy
MH  - Primary Cell Culture
MH  - Rats, Wistar
OTO - NOTNLM
OT  - Arrhythmia
OT  - Fibroblast growth factor 23
OT  - Heart
OT  - Klotho
OT  - Phosphodiesterases
OT  - Renal failure
EDAT- 2020/07/24 06:00
MHDA- 2021/06/29 06:00
CRDT- 2020/07/24 06:00
PHST- 2020/04/01 00:00 [received]
PHST- 2020/07/01 00:00 [accepted]
PHST- 2020/07/24 06:00 [entrez]
PHST- 2020/07/24 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
AID - 10.1007/s00395-020-0810-6 [pii]
AID - 10.1007/s00395-020-0810-6 [doi]
PST - epublish
SO  - Basic Res Cardiol. 2020 Jul 22;115(5):51. doi: 10.1007/s00395-020-0810-6.