Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity
Aim: Myocardial Na<sup>+</sup>/H<sup>+</sup> exchanger-1 (NHE-1) hyperactivity and oxidative stress are interrelated phenomena playing pivotal roles in the development of pathological cardiac hypertrophy and heart failure. Exercise training is effective to convert pathologica...
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| Autores principales: | , , , , |
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| Formato: | Articulo Preprint |
| Lenguaje: | Inglés |
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2018
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| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/100782 https://ri.conicet.gov.ar/11336/95514 https://onlinelibrary.wiley.com/doi/abs/10.1111/apha.13092 |
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I19-R120-10915-100782 |
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dspace |
| institution |
Universidad Nacional de La Plata |
| institution_str |
I-19 |
| repository_str |
R-120 |
| collection |
SEDICI (UNLP) |
| language |
Inglés |
| topic |
Ciencias Médicas Effect on the SHR myocardial NHE-1 IGF-1 |
| spellingShingle |
Ciencias Médicas Effect on the SHR myocardial NHE-1 IGF-1 Yeves, Alejandra M. Burgos, Juan Ignacio Medina, Andrés J. Villa Abrille, María Celeste Ennis, Irene Lucía Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity |
| topic_facet |
Ciencias Médicas Effect on the SHR myocardial NHE-1 IGF-1 |
| description |
Aim: Myocardial Na<sup>+</sup>/H<sup>+</sup> exchanger-1 (NHE-1) hyperactivity and oxidative stress are interrelated phenomena playing pivotal roles in the development of pathological cardiac hypertrophy and heart failure. Exercise training is effective to convert pathological into physiological hypertrophy in the spontaneously hypertensive rats (SHR), and IGF-1—key humoral mediator of exercise training—inhibits myocardial NHE-1, at least in normotensive rats. Therefore, we hypothesize that IGF-1 by hampering NHE-1 hyperactivity and oxidative stress should exert a cardioprotective effect in the SHR. Methods: NHE-1 activity [proton efflux (JH<sup>+</sup>) mmol L<sup>-1</sup> min<sup>-1</sup>], expression and phosphorylation; H<sup>2</sup>O<sup>2</sup> production; superoxide dismutase (SOD) activity; contractility and calcium transients were measured in SHR hearts in the presence/absence of IGF-1. Results: IGF-1 significantly decreased NHE-1 activity (JH<sup>+</sup> at pHi 6.95: 1.39 ± 0.32, n = 9 vs C 3.27 ± 0.3, n = 20, P <.05); effect prevented by AG1024, an antagonist of IGF-1 receptor (2.7 ± 0.4, n = 7); by the PI3K inhibitor wortmannin (3.14 ± 0.41, n = 7); and the AKT inhibitor MK2206 (3.37 ± 0.43, n = 14). Moreover, IGF-1 exerted an antioxidant effect revealed by a significant reduction in H<sup>2</sup>O<sup>2</sup> production accompanied by an increase in SOD activity. In addition, IGF-1 improved cardiomyocyte contractility as evidenced by an increase in sarcomere shortening and a decrease in the relaxation constant, underlined by an increase in the amplitude and rate of decay of the calcium transients. Conclusion: IGF-1 exerts a cardioprotective role on the hypertrophied hearts of the SHR, in which the inhibition of NHE-1 hyperactivity, as well as the positive inotropic and antioxidant effects, emerges as key players. |
| format |
Articulo Preprint |
| author |
Yeves, Alejandra M. Burgos, Juan Ignacio Medina, Andrés J. Villa Abrille, María Celeste Ennis, Irene Lucía |
| author_facet |
Yeves, Alejandra M. Burgos, Juan Ignacio Medina, Andrés J. Villa Abrille, María Celeste Ennis, Irene Lucía |
| author_sort |
Yeves, Alejandra M. |
| title |
Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity |
| title_short |
Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity |
| title_full |
Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity |
| title_fullStr |
Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity |
| title_full_unstemmed |
Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity |
| title_sort |
cardioprotective role of igf-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: a key effect on nhe-1 activity |
| publishDate |
2018 |
| url |
http://sedici.unlp.edu.ar/handle/10915/100782 https://ri.conicet.gov.ar/11336/95514 https://onlinelibrary.wiley.com/doi/abs/10.1111/apha.13092 |
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