Résumé
Heart failure is the inability to maintain a sufficient cardiac output necessary to meet metabolic demand. Cellular compensatory mechanisms, such as the serotonin 4 receptor (5-HT4R) pathway, take place to improve the defective cardiac excitation-contraction coupling (CEC). However, little is known about the regulation of this pathway. Our objective was to investigate the potential involvement of the 5-HT4R partner p11 in the activation of the pathway during heart failure.
Wistar rats underwent ligation of the left coronary artery to mimic infarction. Control Sham-operated animals underwent the same surgery without ligation. Seven weeks post myocardial infarction (PMI) hearts were collected and/or enzymatically digested in order to perform biochemical studies or to assess intracellular calcium (Ca2+) handling at the single cell level. p11 mRNA expression in the left posterior wall was significantly increased at 7 weeks PMI compared to Sham (272±40 vs.141±27 A.U, P<0.05). However, p11 protein levels in 7 weeks PMI myocytes showed a trend toward a decrease compared to sham (0,16±0,02 vs. 0,25±0,09). Interestingly, the expression of the p11 partner Annexin A2 was significantly increased (1,52±0.32 vs. 0,53±0.14, P<0.05) suggesting improved p11 stability. At the CEC level, stimulation of the 5-HT4R pathway by prucalopride did not exert an effect on all CEC parameters evaluated in both PMI and Sham myocytes. Nevertheless, induction of p11 expression by Brain-Derived Neuron Factor treatment in freshly isolated healthy myocytes showed a remarkable increase in Ca2+ transient amplitude (0,27±0,02 vs. 0,18±0,01, P<0.05) and basal Ca2+level (0,67±0,01 vs. 0,64±0,01, P<0.05) following prucalopride stimulation compared to untreated cells.
Cardiac expression of p11 seems to play a role in the modulation of the response to 5-HT4R pathway in both failing and non-failing hearts.