New therapeutic target in heart attack treatment

Myocardial infarction is an important cause of mortality and morbidity worldwide. It is estimated that in a year 3 million people have STEMIs ( ST elevation myocardial infarction)  and 4 million have NSTEMIs ( non-ST elevation myocardial infarction). Emergency treatment is percutaneous coronary intervention ( PCI)  but it is essential that the patients reach the hospital as soon as possible in order to get this treatment. Otherwise, the prognosis is very low because of the heart damage. However, researchers at Temple University School of Medicine have developed a drug that limits the extension of heart injury after heart attack. Laboratory experiments have shown that by blocking a protein called TNNI3K in heart, myocardial lesion is limited; in addition it seems that it protects the heart from a new ischemia.

Ronald Vagnozzi, PhD , lead author on the new study, said that usually what is found in a laboratory cannot be translated in humans, so they wanted to test this new drug in a real scenario. In collaboration with a team of researchers at the Cardiovascular Research Center, Vagnozzi made an experiment on mice that mimicked the blockage of an artery to induce a heart attack; then they administered a drug that inhibits TNNI3K. It appears that cardiac function of mice treated with TNNI3K inhibitor significantly improved compared with the control group, and therefore researchers have thought that this drug may also have beneficial effects in humans.

Vagnozzi said that this protein is found only in the heart, which makes it interesting biologically and therapeutically . He added that even if they do not understand too well the function of this protein, however TNNI3K may be a potential therapeutic target in the treatment of heart attack. Experiments have shown that TNNI3K expression is high in patients with heart failure. Heart failure may be present in patients suffering from heart attack or may develop as a result of this attack.

To investigate the importance of this  overexpression of TNNI3K expression, the researchers created two types of mice : one group of mice with overexpressed TNNI3K and one group of mice in which the protein has been removed. Then they measured the response of the two groups of mice to attack heart. Mice with overexpressed TNNI3K  had a worse prognosis than those with TNNI3K deleted because this protein stimulates heart damage after myocardial damage. It seems that TNNI3K promotes the production of superoxide and activated p38 mitogen -activated protein kinase ( MAPK ), which aggravates ischemia. In contrast, in mice with deleted TNNI3K,  the production of superoxide and MAPK was reduced and heart damage limited.