Spanish researchers have discovered that the degradation of certain proteins after acute myocardial infarction affects the ability of cardioprotection during the restoration of blood flow. Thus, the prevention of the decrease in the levels of GRK2 and AKT proteins would improve cardioprotective mechanisms and reduce myocardial injury and its sequelae.

Studying the molecular mechanisms affected in the early stages after a heart attack is vital to discover new therapeutic strategies aimed at reducing injuries. This has been the objective of a team of the Center for Biomedical Research in Network for Cardiovascular Diseases (CIBERCV) at the Center for Molecular Biology “Severo Ochoa” – Autonomous University of Madrid, IIS La Princesa and Vall d’Hebron Institut de Recerca.

In this work, which has just been published in the journal EBioMedicine, new therapeutic targets related to endogenous cardioprotective mechanisms are proposed to prevent myocardial damage caused in the restoration of blood flow after ischemia.

The collaborative study, in which the groups led by Federico Mayor and Petronila Penela (“Severo Ochoa” Molecular Biology Center, Autonomous University of Madrid and IIS La Princesa) and David Garcia-Dorado and Javier Inserte (Cardiovascular Diseases Group of the Vall d’Hebron Institut de Recerca), reveals previously unnoticed changes in the levels of two cardiac regulatory proteins (GRK2 and AKT) during the early stages of myocardial ischemia-reperfusion, which contribute to the reduction of cardioprotective capacity.

Acute myocardial infarction, due to reduced blood flow to the heart (ischemia), is a major cause of death and disability. Prompt restoration of the circulation is key to reducing the mortality of this event, so the urgent treatment protocols are based on reperfusion with angioplasty (restoration of blood flow by dilated clogged artery) or with the administration of fibrinolytic drugs.

However, despite the advances that allow rapid and effective reperfusion, these clinical procedures can in themselves trigger myocardial damage (reperfusion injury), which leads to a higher prevalence of arrhythmias and heart failure in patients who have survived a heart attack.

Improve cardioprotective capacity

“There are currently no effective therapies to alleviate reperfusion injury, although therapeutic strategies have been postulated to boost the activation of signaling cascades, such as the AKT kinase pathway, which appear to play a cardioprotective role, and thus partially relieve ischemia-reperfusion injury,” explains Petronila Penela, first author of the study.

The new research has focused on this path. Researchers have found in animal models that the levels of GRK2 and AKT proteins, very relevant in cardiovascular pathophysiology, experience a transient decrease in the early stages after the ischemia-reperfusion event.

“These changes deteriorate the overall protective capacity of the AKT pathway to counteract cardiac injury, which leads to increased reperfusion damage,” says Penela. “Our results help to better understand the dynamic regulation of proteins during infarction and could help explain the weakening of cardioprotective pathways during early ischemia-reperfusion,” the say.

These findings open the way for new therapeutic strategies aimed at reducing reperfusion injury, based on enhancing endogenous cardioprotection mechanisms: “The prevention of transient degradation of these proteins during early reperfusion could strengthen cardiac protection therapeutic strategies in the acute myocardial infarction,” the study authors conclude.

 

Source: SINC