Author + information
- Jirapas Sripetchwandee,
- Samuel Kenknight,
- Jantira Sanit,
- Siriporn Chattipakorn and
- Nipon Chattipakorn
Excess cardiac iron deposit from frequent blood transfusion can lead to cardiac dysfunction and fatal arrhythmia, resulting in high mortality in thalassemia major patients. Although mitochondrial dysfunction is linked to these dysfunctions, the effect of iron overload and mitochondrial route of iron entry are still unclear. We hypothesized that iron overload causes cardiac mitochondrial dysfunction, and that mitochondrial calcium uniporter (MCU) is a major route for cardiac mitochondrial iron uptake.
Rat's isolated cardiac mitochondria were incubated with 20-pg/ml Fe2+ for 15 min, and mitochondrial reactive oxygen species (ROS) production, mitochondrial depolarization, and mitochondrial swelling were determined. Pharmacological interventions including MCU blocker (Ru360), mitochondrial permeability transition pore (mPTP) blocker (Cyclosporin A, CsA) and iron chelator (Deferoxamine, DFO) were used to determine the route of mitochondrial iron uptake.
Iron overload caused severe cardiac mitochondrial dysfunction, indicated by markedly increased ROS production, mitochondrial depolarization and mitochondrial swelling (Figure). Although all tested drugs attenuated Fe2+-induced mitochondrial dysfunction, only Ru360 that completely protected cardiac mitochondrial dysfunction.
MCU was the major route for cardiac mitochondrial iron uptake. Blocking MCU could provide a novel therapeutic approach for iron overload cardiomyopathy.
Poster Sessions, Expo North
Sunday, March 10, 2013, 9:45 a.m.-10:30 a.m.
Session Title: Heart Failure: Pharmacologic Therapy
Abstract Category: 17. Heart Failure: Therapy
Presentation Number: 1223-306
- 2013 American College of Cardiology Foundation