Newly Developed Compound Protects Heart Cells During and After Infarction

The compounds also protect against additional damage from restored blood flow after an attack, a process known as reperfusion.

The study, which was led by Dr. Philip LoGrasso, a professor and senior scientific director of discovery biology at the Florida campus of The Scripps Research Institute (TSRI; Jupiter, USA), was published in the February 8, 2013, print edition of the Journal of Biological Chemistry.

A myocardial infarction greatly restricts blood supply, starving heart cells and neighboring tissue of oxygen, which can cause enormous damage in comparatively little time—at times in just a few minutes. This decrease in oxygen, known as an ischemic cascade, results in a sudden crush of metabolic waste that damages cell membranes as well as the mitochondria.

Restoring blood flow adds considerably to the damage, unfortunately, a serious medical issue when it comes to treating major ischemic events such as stroke and heart attack. Reperfusion triggers generation of free radicals and reactive oxygen species that attack and damage cells, intensifying inflammation, signaling white blood cells to attack otherwise salvageable cells and maybe even stimulating potentially lethal cardiac arrhythmias.

The new study revealed that inhibiting the enzyme, c-jun-N-terminal kinase (JNK; pronounced junk), protected against ischemic/reperfusion injury in lab rodents, reducing the total volume of tissue death by as much as 34%. It also substantially decreased levels of reactive oxygen species and mitochondrial dysfunction.

In earlier studies, TSRI scientists discovered that JNK migrates to the mitochondria upon oxidative stress. That migration, combined with JNK activation, they found, is associated with a number of severe health issues, including liver damage, neuronal cell death, stroke, and heart attack. The peptide and small molecule inhibitor (SR3306), developed by Dr. LoGrasso and his colleagues, blocks those harmful effects, thereby reducing programmed cell death four-fold.

“This is the same story,” said Dr. LoGrasso. “These just happen to be heart cells, but we know that oxidative stress kills cells, and JNK inhibition protects against this stress. Blocking the translocation of JNK to the mitochondria is essential for stopping this killing cascade and may be an effective treatment for damage done to heart cells during an ischemic/reperfusion event.”

Moreover, according to Dr. LoGrasso, biomarkers that intensify during a heart attack decrease in the presence of JNK inhibition, a distinct indication that blocking JNK reduces the severity of the infarction.

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