Aortic regurgitation (AR) is the leaking of the aortic valve of the heart that causes blood to flow in the reverse direction that leads to eccentric hypertrophy and can remain asymptomatic for long periods of time. Rheumatic fever (still common in developing countries) and age-related form are the main causes of AR. A very common co-morbidity associated with cardiovascular disease is depression, a state of low mood and aversion to activity that can affect a person's thoughts, behavior, feelings and sense of well-being. Selective serotonin re-uptake inhibitors (SSRI) are widely prescribed as antidepressants. Our laboratory has showed that SSRI treatment (paroxetine) for 4 weeks reduced hypertonic sodium daily intake in rats with sub-chronic AR already with ventricular dilation, and further, prevented ventricular dilation preserving fractional shortening. Actions of oxytocin (OT) centrally as well as peripherally may be involved in this improvement. Natriuretic peptides (ANP and BNP) are associated with OT and may interfere with the expression and regulation of myocardial transcriptional factors, improving cardiac function. The complexity of mechanisms controlling gene expression in this process suggests the involvement of additional regulatory molecules, such as microRNAs; these RNA molecules encoded by the genome regulate the function of skeletal muscle during development and cardiac diseases. Therefore, we propose to study the possible effects of paroxetine treatment for 4 weeks in rats with sub-chronic AR on mRNAs expression of OTR, ANP, BNP, skeletal alpha-actin, alpha- and beta- myosin, as well as the expression of miR-208a - a regulator of cardiac hypertrophy that targets Sox6 and Purb. In addition, we also propose to investigate the effects of OT treatment on OTR, ANP, and BNP mRNAs in a cardiomyocyte cell line (H9c2).
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