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001-es BibID:	BIBFORM030668
Első szerző:	Ait Mou, Younss
Cím:	Beneficial effects of SR33805 in failing myocardium / Ait Mou, Y., Toth, A., Cassan, C., Czuriga, D., de Tombe, P. P., Papp, Z., Lacampagne, A., Cazorla, O.
Dátum:	2011
ISSN:	0008-6363
Megjegyzések:	Aims: SR33805, a potent Ca2+ channel blocker, increases cardiac myofilament Ca2+ sensitivity in healthy rat cardiomyocytes. Therefore, the aim of the present study was to evaluate the effects of SR33805 on contractile properties in ischaemic failing hearts after myocardial infarction (MI) in vivo and in vitro at the cellular level. Methods and results: The effect of SR33805 (10 mM) was tested on the excitation?contraction coupling of cardiomyocytes isolated from rat with end-stage heart failure. Cell shortening and Ca2+ transients were measured in intact cardiomyocytes, while contractile properties were determined in Triton X-100 permeabilized myocytes. Acute treatment with SR33805 restored the MI-altered cell shortening without affecting the Ca2+ transient amplitude, suggesting an increase of myofilament Ca2+ sensitivity in MI myocytes. Indeed, a SR33805-induced sensitization of myofilament activation was found to be associated with a slight increase in myosin light chain-2 phosphorylation and a more significant decrease on troponin I (TnI) phosphorylation. Decreased TnI phosphorylation was related to inhibition of protein kinase A activity by SR33805. Finally, administration of a single intra-peritoneal bolus of SR33805 (20 mg/kg) improved endsystolic strain and fractional shortening of MI hearts. Conclusion: The present study indicates that treatment with SR33805 improved contractility of ischaemic failing hearts after MI in the rat by selectively modulating the phosphorylation status of sarcomeric regulatory proteins, which then sensitized the myofilaments to Ca2+. Our results gave a proof of concept that manipulation of the Ca2+ sensitivity of sarcomeric regulatory proteins can be used to improve contractility of a failing heart.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Myocytes Heart failure Contractile function Sarcomere Ventricular function
Megjelenés:	Cardiovascular Research. - 91 : 3 (2011), p. 412-419. -
További szerzők:	Tóth Attila (1971-) (biológus) Cassan, Cécile Czuriga Dániel (1982-) (kardiológus) de Tombe, Pieter P. Papp Zoltán (1965-) (kardiológus, élettanász) Lacampagne, Alain Cazorla, Olivier
Pályázati támogatás:	INSERM Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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