SAMbA: a novel therapeutic strategy for heart failure with preserved ejection fraction (HFpEF)

• Grant number: 20/04006-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2020
• End date: August 31, 2022
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Julio Cesar Batista Ferreira
• Grantee: Lisley Santos Ramalho
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Heart failure is a degenerative syndrome that affects over 20 million people worldwide, being considered an important health public problem. Overall, 50% of heart failure patients die in the time-window of 5 years after diagnostics. Heart failure is classified into 2 classes: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). HFpEF is a growing epidemiologic problem affecting more than half of the patients with heart failure and identification of novel therapeutic targets that improve HFpEF outcome remains a major priority. Accumulation of fragmented (smaller) mitochondria in the heart is a common feature in patients with either HFpEF or HFrEF. These findings raise the question whether cardiac mitochondrial fragmentation plays a role in HFpEF and whether therapies that inhibit excessive fragmentation have a positive impact on cardiac bioenergetics profile and outcome in HFpEF. We recently demonstrated that SAMbA, a rationally designed synthetic peptide that blocks accumulation of fragmented mitochondria, improves mitochondrial function and cardiac performance in a model of HFrEF in rats. Here, we aim to assess the effectiveness of SAMbA in improving cardiac mitochondrial morphology and bioenergetics, contractility properties and HF outcome in a two-hit model of HFpEF in rats (a combination of high-fat diet and Angiotensin II infusion over 12 weeks). We hypothesize that correcting mitochondrial size and functions with SAMbA will be a useful therapy for patients with HFpEF. This study becomes important since a more detailed understanding of the role of mitochondrial dynamics in HFpEF may contribute to the future use of therapies that act on key mechanisms involved in the pathophysiology of HFpEF, such as the SAMbA molecule. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GONCALVES, LIVIA DE SOUZA; SALES, LUCAS PEIXOTO; SAITO, TIEMI RAQUEL; CAMPOS, JULIANE CRUZ; FERNANDES, ALAN LINS; NATALI, JOSE; JENSEN, LEONARDO; ARNOLD, ALEXANDRE; RAMALHO, LISLEY; BECHARA, LUIZ ROBERTO GRASSMANN; et al. Histidine dipeptides are key regulators of excitation-contraction coupling in cardiac muscle: Evidence from a novel CARNS1 knockout rat model. REDOX BIOLOGY, v. 44, AUG 2021. (17/16540-5, 13/14746-4, 17/11142-1, 13/07937-8, 17/13552-2, 19/24899-9, 18/14544-6, 19/25032-9, 14/11948-8, 20/04006-7)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

RAMALHO, Lisley Santos. SAMβA: a novel therapeutic strategy for heart failure with preserved ejection fraction (HFpEF).. 2022. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.