Stress response and energy metabolism as a function of aging

National Heart, Lung, And Blood Institute

Investigators

Linked publications, trials & patents

Abstract

Aerobic glycolysis and reactive oxygen species (ROS) generation are key drivers of inflammation. Thromboinflammation, a pathologic process fueled by an auto-amplifying loop of ROS, glycolysis, inflammation, and platelet activation, exemplifies this interplay. Here, we report that a central mechanism involves oxidation of voltage-dependent anion channel (VDAC1), which induces VDAC1 oligomerization and mitochondrial membrane permeabilization. We developed IVO-21, a small-molecule therapeutic that binds to oxidized VDAC1. IVO-21 interrupts the thromboinflammatory cycle by preventing inflammation-induced ROS production . Importantly, it achieves these effects without increasing bleeding risk—a major limitation of current anticoagulants. IVO-21 thus represents a mitochondria-targeted therapeutic that preserves mitochondrial function and resolves thromboinflammation safely.