Mitochondrial dysfunction and calcium homeostasis in heart failure: Exploring the interplay between oxidative stress and cardiac remodeling for future therapeutic innovations

Abstract

Heart failure (HF) is a multifaceted clinical syndrome characterized by the heart's inability to pump sufficient blood to meet the body's metabolic demands. It arises from various etiologies, including myocardial injury, hypertension, and valvular heart disease. A critical aspect of HF pathophysiology involves mitochondrial dysfunction, particularly concerning calcium (Ca2+) homeostasis and oxidative stress. This review highlights the pivotal role of excess mitochondrial Ca2+ in exacerbating oxidative stress, contributing significantly to HF progression. Novel insights are provided regarding the mechanisms by which mitochondrial Ca2+ overload leads to increased production of reactive oxygen species (ROS) and impaired cellular function. Despite this understanding, key gaps in research remain, particularly in elucidating the complex interplay between mitochondrial dynamics and oxidative stress across different HF phenotypes. Furthermore, therapeutic strategies targeting mitochondrial dysfunction are still in their infancy, with limited applications in clinical practice. By summarizing recent findings and identifying these critical research gaps, this review aims to pave the way for innovative therapeutic approaches that improve the management of heart failure, ultimately enhancing patient outcomes through targeted interventions.