Fondation Leducq Transatlantic Network of Excellence Targeting Mitochondria to Treat Heart Disease

Abstract

Cell death is a major cause of cardiovascular disease, including myocardial infarction (MI) and heart failure (HF). Despite the progress made during the past 2 decades, acute MI and HF remain major causes of death worldwide. Although mitochondria play a fundamental role in heart physiology and metabolism, they are also key participants in underlying myocyte death after MI by opening of the mitochondrial permeability transition pore (PTP). The PTP, in which an inner membrane channel opens in response to increased matrix Ca2+ and reactive oxygen species (ROS), appears to be a universal mediator of regulated necrosis, and both Ca2+ and ROS are known to become dysregulated during MI and HF. Therefore, small molecule inhibitors of PTP are promising targets for the treatment of cardiovascular disease.