2014
DOI: 10.1172/jci64784
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Abstract: PKA phosphorylates multiple molecules involved in calcium (Ca 2+ ) handling in cardiac myocytes and is considered to be the predominant regulator of β-adrenergic receptor-mediated enhancement of cardiac contractility; however, recent identification of exchange protein activated by cAMP (EPAC), which is independently activated by cAMP, has challenged this paradigm. Mice lacking Epac1 (Epac1 KO) exhibited decreased cardiac contractility with reduced phospholamban (PLN) phosphorylation at serine-16, the major PKA… Show more

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Cited by 94 publications
(149 citation statements)
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“…We did not study the role of the two isoforms in our work but assessed the overall effect of Epac activation. The two isoforms are believed to have different sub‐cellular localization, expression and function (Okumura et al, 2014). This has been widely investigated within the mouse heart (Schmidt et al, 2013).…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…We did not study the role of the two isoforms in our work but assessed the overall effect of Epac activation. The two isoforms are believed to have different sub‐cellular localization, expression and function (Okumura et al, 2014). This has been widely investigated within the mouse heart (Schmidt et al, 2013).…”
Section: Discussionmentioning
confidence: 99%
“…Although most of the biological effects of cAMP on the heart have been assigned to PKA (Bers, 2007), cAMP also activates Epac (a guanine nucleotide exchange protein directly activated by cAMP) (de Rooij et al, 1998). The cAMP/Epac pathway is independent of and parallel to the cAMP/PKA signalling pathway (Pereira et al, 2012; Okumura et al, 2014). Therefore, availability of cell‐permeable cAMP analogues allowing selective activation of either PKA or Epac represents a valuable tool to identify the involvement and the contribution of these cAMP sensors in cardioprotection (Dudley et al, 2014).…”
Section: Introductionmentioning
confidence: 99%
“…Even though Epac2 inhibition suppresses the effect of PDE4 inhibition, we cannot formally exclude the possibility that some of the effects are due to Epac1. It was recently reported that Epac1 regulates PLB phosphorylation and Ca 2+ handling in the heart through a PLB/PKC pathway (39). PDE4D gene inactivation causes two major cardiac phenotypes: increased propensity to arrhythmias and late-onset dilated cardiomyopathy (18,20).…”
Section: +mentioning
confidence: 99%
“…Les souris Epac1 -/-et Epac2 -/-, ainsi que les doubles knock-out, ne présentent aucune anomalie cardiaque. Ces isoformes ne semblent donc pas indispensables au développement du myocarde et au maintien de la fonction cardiaque à l'état basal [29][30][31]. Seule la délétion de Epac1 réduit le remodelage pathologique induit par l'activation chronique des -AR, ce qui confirme l'importance de Epac1 dans la signalisation -adrénergique au cours de l'hypertrophie cardiaque pathologique.…”
Section: Epac1 Et Remodelage Pathologique Cardiaqueunclassified
“…Seule la délétion de Epac1 réduit le remodelage pathologique induit par l'activation chronique des -AR, ce qui confirme l'importance de Epac1 dans la signalisation -adrénergique au cours de l'hypertrophie cardiaque pathologique. Toutefois, dans un autre modèle d'hypertrophie cardiaque induite par une sténose aortique, l'absence de Epac1 ne prévient pas l'hypertrophie cardiaque, mais seulement la fibrose et l'apoptose des cardiomyocytes, ce qui suggère que les effets cardioprotecteurs de Epac1 vis-à-vis de l'hypertrophie cardiaque dépendent de la nature du stress [30].…”
Section: Epac1 Et Remodelage Pathologique Cardiaqueunclassified