New breakthrough may lead to new treatment for heart attacks
Washington: A recent study has revealed that it is possible to limit the extent of damage during and after a heart attack.
Experiments done by researchers on mice, at Temple University School of Medicine, showed that that inhibition of a heart protein called TNNI3K reduced damage from heart attack and protected the heart from further injury.
Ronald Vagnozzi,, PhD, lead author on the new study, and his team created a real-world clinical scenario in mice by mimicking blockage of an artery to induce heart attack and then administering a TNNI3K inhibitor.
When cardiac function was subsequently improved in treated mice versus untreated controls, Vagnozzi and colleagues realized that a TNNI3K inhibitor could have important clinical benefits for human patients.
The researchers found that TNNI3K expression is elevated in patients who are suffering from heart failure, which can develop in the years following heart attack. To explore the significance of that elevation, they engineered mice to overexpress TNNI3K.
They also created a second set of engineered mice, in which the protein was deleted. They then measured the animals' response to heart attack.
When overexpressed, Vagnozzi and colleagues found that TNNI3K promoted the injury of heart tissue from ischemia (blockage of blood flow) and reperfusion (restoration of blood flow) during and after a heart attack.
TNNI3K overexpression in heart cells encouraged the production of superoxide, a reactive molecule from mitochondria, and activated p38 mitogen-activated protein kinase (MAPK), an enzyme that responds to stress signals in cells.
The combined result of those activities was impaired mitochondrial function and heart cell death, which worsened ischemia/reperfusion injury.
The opposite occurred in mice in which TNNI3K had been deleted-superoxide production and p38 activation were reduced, and injury to the heart was limited. Reductions in heart dysfunction and fibrosis (hardening of heart tissue) were also observed.
The study has been published in journal Science Translational Medicine.