Banca de QUALIFICAÇÃO: ALINE MARIA BRITO LUCAS

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : ALINE MARIA BRITO LUCAS
DATE: 09/06/2023
TIME: 14:00
LOCAL: Google meet
TITLE:

MITOCHONDRIAL EFFECTS OF CALORIC RESTRICTION DURING CARDIAC HYPERTROPHY

KEY WORDS:

mitochondria, caloric restriction, cardiac hypertrophy, oxidative stress, free radicals, adrenergic signaling.

PAGES: 67
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Cardiac hypertrophy is characterized by an increase in heart size due to intracellular stimuli acquired from pressure or volume overload. Although cardiac hypertrophy is an adaptive and transient response, it often evolves into congestive heart failure, causing heart failure. Mitochondrial dysfunctions are involved in the development of cardiac pathologies and are generally associated with defects in the electron transport chain, calcium overload, reactivation of fetal genes and, mainly, increased oxidative stress. Caloric restriction is a nutritional intervention that protects against cardiac hypertrophy by decreasing oxidative stress and improving mitochondrial function. However, the mechanisms involved in the cardiovascular protective effects of caloric restriction are still under investigation. In this study, we show that this dietary intervention prevents cardiac protein elevation, prevents fetal gene (atrial natriuretic factor) reprogramming, and blocks the increase in heart weight ratio per tibial length (HW/TL) seen in induced cardiac hypertrophy by isoproterenol. Our findings suggest that caloric restriction inhibits pathological cardiac growth, while reducing mitochondrial reverse electron transport-induced hydrogen peroxide formation and improving mitochondrial content. Additionally, caloric restriction attenuated the opening of the Ca2+-induced mitochondrial permeability transition pore in mitochondria isolated from mice treated with isoproterenol. We also found that calorie restriction blocked the negative correlation of antioxidant enzymes (superoxide dimutase and glutathione peroxidase activity) and HW/TL, leading to maintenance of sulfhydryl and glutathione protein levels. Given the nature of isoproterenol-induced cardiac hypertrophy, we investigated whether caloric restriction might alter cardiac β-adrenergic sensitivity. Using isolated rat hearts in a Langendorff system, we found that calorie-restricted rats (similar to controls) preserved β-adrenergic signaling. On the other hand, hypertrophic hearts (treated for seven days with isoproterenol) were insensitive to β-adrenergic activation with isoproterenol (50 nM). Despite protecting against cardiac hypertrophy, caloric restriction did not change the lack of response to isoproterenol in isolated hearts harvested from hypertrophic rats. These results suggest (through a series of mitochondrial, oxidative stress and cardiac hemodynamic studies) that caloric restriction has beneficial effects against hypertrophic cardiomyopathy and may contribute to the elucidation of new therapeutic routes for the prevention and/or treatment of complications related to hypertrophy. heart disease and other cardiovascular diseases.

BANKING MEMBERS:
Interno - FRANCISCO NASCIMENTO PEREIRA JUNIOR
Presidente - HEBERTY DI TARSO FERNANDES FACUNDO
Interno - MARCOS ANTONIO PEREIRA DE LIMA
Interno - THIAGO MIELLE BRITO FERREIRA OLIVEIRA