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| Author(s): |
Vitor Loureiro da Silva
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Botucatu. 2019-04-16. |
| Institution: | Universidade Estadual Paulista (Unesp). Faculdade de Medicina. Botucatu |
| Defense date: | 2019-03-01 |
| Advisor: | Antonio Carlos Cicogna |
| Abstract | |
Introduction: Several experimental models have been proposed for the study of cardiac remodeling (CR); among them, the induction of supravalvular aortic stenosis (AoS). The pathophysiological mechanisms responsible for the cardiac function depression include changes in calcium (Ca2+) and its regulatory proteins. Exercise training (ET) has been used in the management of cardiopathies. In cardiac pathology due to pressure overload, ET completely or partially restores the activity and/or expression of regulatory proteins of Ca2+ handling, optimizing intracellular Ca 2+ flow and attenuating cardiac functional impairment. Objective: To analyze the participation of Ca2+ handling and its regulatory proteins in the improvement of the cardiac function of rats with aortic stenosis and ventricular dysfunction by ET. Material and Methods: Male Wistar rats (70-90 g) submitted to supravalvular aortic stenosis (AoS) were divided into two groups: operated control (Sham) and aortic stenosis (AoS). After 18 weeks of the surgical procedure, cardiac function analysis was performed for redistribution of the groups: non-exposed to exercise training (Sham, n = 36 and AoS, n = 29) and trained (ShamET, n = 33 and AoSET, n = 32) for 10 weeks. The treadmill exercise training was performed with a velocity equivalent to the lactate threshold, obtained during effort tests (initial, 4th and 7th weeks, and final). CR was evaluated by echocardiography, papillary muscle and cardiomyocyte isolated and postmortem macroscopy. The myocardial calcium handling was analyzed by the elevation of extracellular calcium, post-pause potentiation and Ca2+ pump blockade of the sarcoplasmic reticulum (SERCA2a), by cyclopiazonic acid, and L-type calcium channels by diltiazem in the papillary muscle and by the isolated cardiomyocyte. Expression of the proteins involved in Ca2+ handling was evaluated by Western Blot. The results were discussed at a significance level of 5%. Results: At the 18th week, before the ET, the AoS animals presented concentric left ventricular hypertrophy, diastolic and systolic dysfunction and intolerance to physical exercise. The ET attenuated the diastolic dysfunction 9 and benefited the systolic function of the animals with pressure overload. AoSET animals presented better response to post-pause potentiation and SERCA2a blockade than the AoS, suggesting a positive adaptation to the Ca2+ recapture by the sarcoplasmic reticulum. After inhibition of the L-type calcium channels there was a difference in response between the AoS and AoSET groups, which also suggested better SERCA2a activity. In the cardiomyocyte analysis, the ET was able to improve aspects of the mechanical function and the responsiveness of the myofilaments to the Ca2+ of the AoS animals. AoS animals presented alteration in the protein expression of the Rianodine Receptor, SERCA2a and NCX, and ET restored SERCA2a and NCX levels near normal values. Conclusion: Positive adaptations in the Ca2+ handling and its regulatory proteins by ET participate in the attenuation of ventricular dysfunction in rats with supravalvar aortic stenosis. (AU) | |
| FAPESP's process: | 15/20013-5 - Participation of calcium transient and their regulatory proteins in cardiac function improvements in rats with supravalvar aortic stenosis and ventricular dysfunction submitted to exercise training |
| Grantee: | Vitor Loureiro da Silva |
| Support Opportunities: | Scholarships in Brazil - Doctorate |