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Involvement of protein kinase C βII in heart failure

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Author(s):
Julio Cesar Batista Ferreira
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Escola de Educação Física e Esportes (EEFE/BT)
Defense date:
Examining board members:
Patricia Chakur Brum; Kleber Gomes Franchini; Alessandra Medeiros; Carlos Eduardo Negrão; Deborah Schechtman
Advisor: Patricia Chakur Brum
Field of knowledge: Biological Sciences - Physiology
Indexed in: Banco de Dados Bibliográficos da USP-DEDALUS; Biblioteca Digital de Teses e Dissertações - USP
Location: Universidade de São Paulo. Biblioteca da Escola de Educação Física e Esporte; T 616.12 F-7
Abstract

Heart failure is a common endpoint for many forms of cardiovascular disease and a significant cause of morbidity and mortality worldwide. Protein kinase C isozymes emerge as important potential therapeutic targets in chronic cardiovascular disease. However, individual PKC isozymes play different roles in the pathogenesis of cardiac diseases. Here, we characterized the cardiac phenotype as well as the different PKC isozyme activation profile during myocardial-induced heart failure progression in rat. Furthermore, we evaluated the role of selective PKCβ II inhibition on survival, left ventricle remodeling and cardiac function in myocardial-induced heart failure. Moreover, we identified the cardiac PKCβII substrates related to heart failure. Finally, PKCβII and PKCβI specific inhibitors were chronically delivered to hypertensive-induced heart failure rats and the cardiac phenotype was evaluated. Our data suggest that 6-wks of PKCβII inhibition, but not PKCβI, improved animal survival by restoring cardiac function and promoting cardiac anti-remodeling effect in both myocardial infarctioninduced heart failure and hypertensive-induced heart failure rats. The improved cardiac function and anti-remodeling effect of PKCβII inhibition seems to be associated with increased contractility of cardiac myocytes, improved miofilaments/Ca2+ sensitivity and decreased cardiac inflammatory response. Altogether, the results provide evidence for beneficial effects of PKCβII specific intracellular inhibition on cardiac function and remodeling, which may be a promising cellular therapy for heart failure treatment (AU)

FAPESP's process: 06/56321-6 - Involvement of protein kinase C βII and ε isoforms in heart failure induced by myocardial infarction
Grantee:Julio Cesar Batista Ferreira
Support Opportunities: Scholarships in Brazil - Doctorate