Apelin/APJ signaling in IGF-1-induced acute mitochondrial and antioxidant effects in spontaneously hypertensive rat myocardium

• Autores: Yeves, Alejandra del Milagro; Godoy Coto, Joshua; Pereyra, Erica Vanesa; Medina, Andrés Javier; González Arbeláez, Luisa Fernanda; Cavalli, Fiorella Anabel; Ennis, Irene Lucía
• Año de publicación: 2024
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Ciencias Médicas; apelin-13; SHR; IGF-1
• Institución: Universidad Nacional de La Plata

IGF-1 and apelin are released in response to exercise training with beneficial effects. Previously we demonstrated that a swimming routine is effective to convert pathological into physiological cardiac hypertrophy, and that IGF-1 improves contractility and the redox state, in spontaneously hypertensive rats (SHR). Now, we hypothesize that the apelinergic pathway is involved in the cardioprotective effects of IGF-1 in the SHR. We assessed the redox state and mitochondrial effects of IGF-1 or apelin in the presence/absence of AG1024 or ML221 [pharmacological antagonists of IGF1 (IGF1R) and apelin (APJ) receptors, respectively] in SHR isolated cardiomyocytes or perfused hearts. Acute IGF-1 (10 nmol/L) significantly: -reduced H2O2 production (IGF-1:62±6; control:100±8.1, %), -increased the activity of superoxide dismutase (IGF-1:193±17, control: 100±13,%), -prevented H2O2-induced m loss (TMREF10min/F0 min: IGF-1:0.93±0.017, control: 0.72±0.029), –reduced mitochondrial permeability transition pore (mPTP) opening estimated by the calcium retention capacity (nmol/mg protein, IGF-1:251±34, control:112±5), and -increased P-AMPK (IGF-1:129±0.9, control: 100±2%) and P-AKT (IGF-1:143±17 control:100±6, %). These effects were suppressed not only by the antagonism of IGF1R but also of APJ. Moreover, IGF-1 significantly increased APJ (IGF-1:198±29 control:100±15,%) and apelin mRNAs (IGF-1:251±48, control:100±6,%). On the other hand, an equipotent dose of exogenous apelin (50 nmol/L) emulated IGF-1 effects being cancelled by the antagonism of APJ however not by AG1024. IGF-1/IGF1R stimulates the apelinergic pathway, improving the redox balance and mitochondria status in the pathologically hypertrophied myocardium of the SHR
Facultad de Ciencias Médicas
Centro de Investigaciones Cardiovasculares