Cardiovascular disease is one of the most common causes of death in the world. Although we have many treatments against the various conditions, many studies show that incidences of cardiac-related issues will only rise over the next few decades.
Heart attacks are one of the more commonly known cardiovascular diseases. They are characterized by restricted blood flow to the heart’s tissue, leading to isolated areas of tissue death. The areas of dead tissue are called a myocardial infarct, and a rapid response is needed to prevent the spread of tissue death.
The problem with a rapid response is that it can also cause damage. Ischemia-reperfusion injury is when an area of the body that has been starved of oxygen suddenly receives a surge of oxygen-rich blood. This can cause the cells of the area, which were in a state of starvation, into a state of shock and force a type of controlled cell death. Scientists have been trying to tackle this issue for years, but a new study from the Universite de Montpellier in France might have a solution.
Their idea was to use something called a peptide (a type of small protein) to prevent the shock-induced cell death that often comes after heart attack recovery. In a previous study, they had developed a peptide to target a protein called DAXX, which they had found to be an important player in ischemia-reperfusion injury and could reduce the area of tissue damage by up to 48% in a mouse model. This new study sought to examine the long term effects of using this peptide, termed TD (Tat-DAXXp), to protect the heart after a heart attack in a mouse model.
The team began by measuring a biomarker cardiac troponin, a standard indicator of infarct size, in TD treated and control groups. The only change they saw was in the immediate aftermath of the heart attack, where the untreated group had much larger troponin levels (coinciding with a higher fatality rate). Measurements of heart function told a different story, as, at almost every monthly checkup, the TD-treated mice had stronger hearts. TD-treatment even suppressed cardiac fibrosis, another common side effect of various cardiovascular diseases.
This study showed that in a relevant mouse model, the peptide Tat-DAXXp could improve the long-term outcomes after a heart attack. The mechanism behind Tat-DAXXp was previously revealed to be the prevention of the innate cell death pathway controlled in part by the protein DAXX. These positive results, combined with previous findings, suggest TD may be a strong candidate for clinical trials in the future.
The study concludes, “In conclusion, a single dose of TD peptide prior to reperfusion decreases infarct size assessed by cTnI quantification and induces a restoration of cardiac performance together with a prevention of post-MI LV remodeling.”