Mecanismos moleculares envolvidos na hipertrofia cardíaca em ratos com regurgitação aórtica tratados com paroxetina

• Ano de defesa: 2015
• Autor(a) principal: Omoto, Ana Carolina Mieko [UNESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Estadual Paulista (Unesp)
• Palavras-chave em Português: Coração - Hipertrofia; Coração - Doenças - Aspectos nutricionais; Insuficiência aórtica - Aspectos nutricionais; Antidepressivos; Expressão gênica; Heart - Diseases; Gene expression
• Link de acesso: http://hdl.handle.net/11449/144034; http://www.athena.biblioteca.unesp.br/exlibris/bd/cathedra/23-08-2016/000868433.pdf

Aortic regurgitation (AR) causes volume overload to the heart culminating with left ventricle dilation and eccentric hypertrophy. A very common co-morbidity associated with cardiovascular disease is depression. Selective serotonin re-uptake inhibitors (SSRI) are widely prescribed as antidepressants. Our laboratory has showed that paroxetine (parox), an SSRI, treatment for 4 weeks prevented ventricular dilation preserving fractional shortening. Neurohumoral and peripheral changes might be involved in this improvement. Our hypothesis is that parox could act indirectly, in a oxytocin-dependent manner, or directly in the heart. Trying to understand the mechanism involved in the improvement of fractional shortening, we verify the expression of several genes involved in heart hypertrophy in vivo and in vitro. For the in vivo studies male Wistar rats (280-300kg) were submitted to AR surgery, by retrograde puncture of the aortic valves leaflets, or sham surgery. Morphofunctional variables of the hearts were analyzed by echocardiograms at week 4 and 8. The animals were divided in 4 groups: AR+Parox, AR+Saline, Sham+Parox and Sham+Saline. Parox (10mg/kg) was administered subcutaneously for 4 weeks and saline was used as control. At week 8 the animals were euthanized for tissue collection and posterior analysis of hypertrophic markers gene expression by RTq-PCR. To investigate the effects of parox in vitro we use H9c2 cell line. This cells were pre-treated or not with phenilephrine (phenil, 100μM), an α-adrenergic agonist, and then parox (300μM) was added to the culture. Our results show that AR model was able to produce morphofunctional changes, related to volume overload, in the heart and increase gene expression of cardiac hypertrophy markers. In addition, AR+Parox group preserved fractional shortening (45,67±1,52 vs 31,97±3,08) and decrease gene expression of β-MyHC (1,45±0,14 vs 1,97±0,15), microRNAs - 208b (1,29±0,09 vs 2,37±0,09) and...