The effect of the sphingosine-1-phosphate analogue FTY720 on
atrioventricular nodal tissue

J 2015

The effect of the sphingosine-1-phosphate analogue FTY720 on atrioventricular nodal tissue

EGOM, Emmanuel E., Peter KRUŽLIAK, Vladimír ROTREKL a Ming LEI

Základní údaje

Originální název

The effect of the sphingosine-1-phosphate analogue FTY720 on atrioventricular nodal tissue

Autoři

EGOM, Emmanuel E. (124 Kanada), Peter KRUŽLIAK (203 Česká republika), Vladimír ROTREKL (203 Česká republika, garant, domácí) a Ming LEI (826 Velká Británie a Severní Irsko)

Vydání

Journal of Cellular and Molecular Medicine, Hoboken, Wiley-Blackwell, 2015, 1582-4934

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

Genetika a molekulární biologie

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 4.938

Kód RIV

RIV/00216224:14110/15:00085124

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1111/jcmm.12549

UT WoS

000357031200027

Klíčová slova anglicky

fingolimod; atrioventricular node; sphingosine-1-phosphate

Štítky

EL OK

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 30. 12. 2015 14:51, Ing. Mgr. Věra Pospíšilíková

Anotace

V originále

The sphingosine-1-phosphate (S1P) receptor modulator, fingolimod (FTY720), has been used for the treatment of patients with relapsing forms of multiple sclerosis, but atrioventricular (AV) conduction block have been reported in some patients after the first dose. The underlying mechanism of this AV node conduction blockade is still not well-understood. In this study, we hypothesize that expression of this particular arrhythmia might be related to a direct effect of FTY720 on AV node rather than a parasympathetic mimetic action. We, therefore, investigated the effect of FTY720 on AV nodal, using in vitro rat model preparation, under both basal as well as ischaemia/reperfusion conditions. We first look at the expression pattern of S1P receptors on the AV node using real-time PCR. Although all three S1P receptor isoforms were expressed in AVN tissues, S1P1 receptor isoform expression level was higher than S1P2 and S1P3. The effect of 25nM FTY720 on cycle length (CL) was subsequently studied via extracellular potentials recordings. FTY720 caused a mild to moderate prolongation in CL by an average 9% in AVN (n=10, P<0.05) preparations. We also show that FTY720 attenuated both ischaemia and reperfusion induced AVN rhythmic disturbance. To our knowledge, these remarkable findings have not been previously reported in the literature, and stress the importance for extensive monitoring period in certain cases, especially in patients taking concurrently AV node blocker agents.

Citovat

EGOM, Emmanuel E., Peter KRUŽLIAK, Vladimír ROTREKL a Ming LEI. The effect of the sphingosine-1-phosphate analogue FTY720 on atrioventricular nodal tissue. Journal of Cellular and Molecular Medicine. Hoboken: Wiley-Blackwell, 2015, roč. 19, č. 7, s. 1729-1734. ISSN 1582-4934. Dostupné z: https://dx.doi.org/10.1111/jcmm.12549.

@article{1320433,
   author = {Egom, Emmanuel E. and Kružliak, Peter and Rotrekl, Vladimír and Lei, Ming},
   article_location = {Hoboken},
   article_number = {7},
   doi = {http://dx.doi.org/10.1111/jcmm.12549},
   keywords = {fingolimod; atrioventricular node; sphingosine-1-phosphate},
   language = {eng},
   issn = {1582-4934},
   journal = {Journal of Cellular and Molecular Medicine},
   title = {The effect of the sphingosine-1-phosphate analogue FTY720 on atrioventricular nodal tissue},
   volume = {19},
   year = {2015}
}

TY  - JOUR
ID  - 1320433
AU  - Egom, Emmanuel E. - Kružliak, Peter - Rotrekl, Vladimír - Lei, Ming
PY  - 2015
TI  - The effect of the sphingosine-1-phosphate analogue FTY720 on atrioventricular nodal tissue
JF  - Journal of Cellular and Molecular Medicine
VL  - 19
IS  - 7
SP  - 1729-1734
EP  - 1729-1734
PB  - Wiley-Blackwell
SN  - 15824934
KW  - fingolimod
KW  - atrioventricular node
KW  - sphingosine-1-phosphate
N2  - The sphingosine-1-phosphate (S1P) receptor modulator, fingolimod (FTY720), has been used for the treatment of patients with relapsing forms of multiple sclerosis, but atrioventricular (AV) conduction block have been reported in some patients after the first dose. The underlying mechanism of this AV node conduction blockade is still not well-understood. In this study, we hypothesize that expression of this particular arrhythmia might be related to a direct effect of FTY720 on AV node rather than a parasympathetic mimetic action. We, therefore, investigated the effect of FTY720 on AV nodal, using in vitro rat model preparation, under both basal as well as ischaemia/reperfusion conditions. We first look at the expression pattern of S1P receptors on the AV node using real-time PCR. Although all three S1P receptor isoforms were expressed in AVN tissues, S1P1 receptor isoform expression level was higher than S1P2 and S1P3. The effect of 25nM FTY720 on cycle length (CL) was subsequently studied via extracellular potentials recordings. FTY720 caused a mild to moderate prolongation in CL by an average 9% in AVN (n=10, P<0.05) preparations. We also show that FTY720 attenuated both ischaemia and reperfusion induced AVN rhythmic disturbance. To our knowledge, these remarkable findings have not been previously reported in the literature, and stress the importance for extensive monitoring period in certain cases, especially in patients taking concurrently AV node blocker agents.
ER  -

EGOM, Emmanuel E., Peter KRUŽLIAK, Vladimír ROTREKL a Ming LEI. The effect of the sphingosine-1-phosphate analogue FTY720 on atrioventricular nodal tissue. \textit{Journal of Cellular and Molecular Medicine}. Hoboken: Wiley-Blackwell, 2015, roč.~19, č.~7, s.~1729-1734. ISSN~1582-4934. Dostupné z: https://dx.doi.org/10.1111/jcmm.12549.

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