Does apelin mediate the cardioprotective effects of IGF-1?

CAVALLI F.,; GODOY COTO J.; ENNIS I.L.; YEVES A.M.,; PEREYRA ERICA

Berlin

Congreso; XXIV World Congress of International Society for Heart Research; 2022

International Society for Heart Research

Does apelin mediate the cardioprotective effects of IGF-1? 2500 CHARACTERS INCLUDING SPACES)Yeves AM, Godoy Coto J, Cavalli F, Pereyra E, Ennis IL. Hypertension is a significant health risk that affects millions of people worldwide. It has been well established that patients with hypertensive cardiac hypertrophy die most frequently because of heart failure. Hypertensive myocardium is associated to mitochondrial dysfunction and redox disbalance. On the other hand, exercise training produces several beneficial effects, usually mediated by humoral factors. In this sense, apelin and insulin like growth factor-1 (IGF-1) increase in response to exercise exerting cardioprotective effects. Particularly, whether apelin mediates the cardioprotective effects of IGF-1 by an autocrine paracrine mechanism is not clear yet. Objective. To determine the acute myocardial effects of apelin or IGF-1 on oxidative stress and mitochondrial status, as well as the possible crosstalk between the signaling pathways triggered by both humoral factors. Methods. 3-month-old SHR isolated hearts or isolated cardiomyocytes were perfused 10 min in presence or absence of apelin, IGF-1 and the specific antagonist of their receptors (AG1024 and ML221 for IGF1R and APJ, respectively). We mainly explored the effects on reactive oxygen species (ROS) production, antioxidant activity, mitochondrial function, and the crosstalk between IGF-1 and apelin signaling. Results. IGF-1 and apelin increased myocardial SOD activity (U/mg, IGF-1: 59.8±5.2, Apelin: 56±3.9 vs Control: 41.6±3) and decreased ROS production (%, IGF-1: 64.6±8.6, Apelin: 59.6± 5.4 vs Control: 100±8.3). Interestingly, both agents prevented  loss induced by H2O2 (IGF-1: 0.917±0.021, Apelin: 0.984±0.024 vs Control: 0.827±0.024) and inhibited mPTP opening (CRC, IGF-1: 289±11, Apelin: 292±23 vs Control: 142±28). The antagonism of IGF1R (AG1024) or of APJ (ML221) cancelled all these beneficial effects. Interestingly, exogenously administrated IGF-1 increased the mRNA cardiac expression of APJ (IGF-1: 175.8±27.7 vs Control: 100±16), similarly to the effect of swim training, were it is well known that an increase in IGF-1 takes place (Apelin mRNA: trained: 121.7±3.3 vs Sed: 100±5.3; APJ mRNA: trained: 211±38.3 vs Sed 100±3; APJ protein: trained: 159.26±8.8 vs Sed: 100±9.57). Even more, the mitochondrial protective effects induced by IGF-1 were prevented by the pharmacological inhibition of APJ (IGF-1+ML221, SOD activity: 43.28±2.75, CRC: 57±7). In conclusion, our preliminary data suggest that apelin/APJ may be an intermediate step in the signaling cascade trigger by IGF-1 responsible for cardioprotection.