Drug heals broken heart
28.05.2013 - Researchers have presented new preclinical data on a mitochondria-protecting drug that could reduce tissue damage following heart attacks.
During a heart attack, the major vessels that supply the heart with blood become blocked, preventing oxygen from reaching an area of the heart tissue. When the patient reaches hospital, doctors remove the blockage using medicines or surgery and restore blood flow to the heart, however in almost 100% of cases, tissue damage occurs when blood flow is restored.
A team headed by Michael Murphy has now unravelled how the novel mitochondria-selective S-nitrosating agent, MitoSNO, protects the heart from oxidative damage, which occurs when blood flow is restored after infarction (Nature Medicine ). In a mouse model, they found that S-nitrosation of the mitochondrial complex I slows the reactivation of mitochondria during the crucial first minutes of the reperfusion of ischemic tissue, thereby decreasing ROS production, oxidative damage and tissue necrosis.
MitoSNO works by briefly ‘switching off’ the mitochondria in the first few minutes after blood flow is returned to prevent a build-up of free radicals that can kill heart cells through apoptosis. To achieve this, MitoSNO is designed to accumulate inside heart mitochondria rapidly after its injection into the blood. In detail, MitoSNO1-induced production of nitric oxide radicals reversibly inhibits respiration at cytochrome c oxidase and increased extracellular oxygen concentration under hypoxic conditions.
Dr Mike Murphy from the MRC Mitochondrial Biology Unit, who led the study, said: “When cells are starved of oxygen for any length of time, they begin to shut down. When blood rushes back, the mitochondria go into over-drive, churning out free radicals that cause the cells to die. MitoSNO effectively flicks a switch in the mitochondria, slowing down reactivation during those critical first minutes when blood flow returns and protecting the heart tissue from further damage. The researchers now hope to secure funding to test their new compound in early human studies.