Metabolic Resuscitation in Heart Failure.

PROJECT DESCRIPTION/ABSTRACT The heart requires a constant supply of ATP to meet its high energy demands and maintain its contractile function. The relationship between cardiac energy deficiency and heart failure has been extensively studied, leading to various strategies to improve energy deficiency in heart failure. However, despite these efforts, limitations persist, and the energy deficit in failing hearts remains. A more comprehensive understanding that moves beyond our current linear model of energy production and consumption is needed to address this challenge. In this project, the investigators proposed exploring the metabolic resuscitation system, a revival mechanism profoundly downregulated in heart failure patients. The overarching objective of this program is to determine the connection between a compromised metabolic resuscitation system and the pathogenesis of heart failure and revival. Comprehensive experimental approaches and patient-related genetic animal models are applied to investigate this new system. The eventual results will allow a look from a different angle to understand the progression of HF. Manipulating the novel factors in this system could be a novel therapeutic strategy and potential new biomarkers for heart failure treatment and prevention, eventually improving heart failure patient outcomes. The project expects to achieve three main objectives: defining the functional and pathological significance of this system in the heart, uncovering the regulation of this resuscitative mechanism, and exploring its translational potential for preventing and treating heart failure patients.