An investigation carried out by the teams of Guadalupe Sabio And Jose Jalife at the National Cardiovascular Research Center of Madrid (CNIC) has discovered a new signaling pathway that is behind the occurrence of Ventricular fibrillation, a form of cardiac arrhythmia. The work that has just been published in the journal Nature cardiovascular research offers new hope for combating this potentially fatal disease.
Ventricular fibrillation is the most common immediate cause of sudden cardiac death. Although age is one of the best known risk factors for the development of cardiac arrhythmias, the mechanisms behind this association are still unclear and complicate the development of cardiac arrhythmias. specific treatment development.
The heart beats regularly and in a coordinated manner to pump blood efficiently throughout the body. To do this, it must coordinate the contraction of all of its cells and each heartbeat must follow a carefully orchestrated pattern. When an arrhythmia occurs, the heart rhythm changes, speeds up, becomes irregular, and can be potentially fatal.
Optical mapping images of two different hearts from mice that developed ventricular fibrillation. / CNIC
Study Rodent modelsCNIC researchers discovered the connection between the stress protein kinases p38γ and p38δ and the development of ventricular fibrillation, regardless of gender.
This discovery opens new avenues for possible therapeutic interventions in this pathology.
Crucial role in the development of arrhythmias
The researchers observed that activation of p38γ and p38δ increased in the hearts of people old mices and those with genetic or drug-induced diseases that predispose to arrhythmias, suggesting that this pathway played a critical role in the development of this disease.
The authors discovered the connection between the stress protein kinases p38γ and p38δ and the development of ventricular fibrillation, regardless of gender
Accordingly Rafael RomeroFirst signatory of the article and CNIC researchers: “When we realized that activation of these p38s is common in various arrhythmogenic situations, we knew that they could play a key role that needed to be investigated.”
Comprehensive study of this signaling pathway revealed that when activated, these protein kinases alter the electrical properties of cardiomyocytes, leading to the occurrence of arrhythmias. This happens by changing existing ion channels in the heart muscle cells, which are responsible for coordinating cell contraction.
The researchers found that p38γ and p38δ phosphorylate the ryanodine receptor 2 (RyR2) and the SAP97 protein, disrupting the localization of the Kv4.3 channel. presents them as new substrates of p38γ and p38δ. Ultimately, these molecular changes led to the appearance of premature ventricular activity and increased susceptibility to ventricular fibrillation.
These findings could open up new perspectives for the pReversal of persistent ventricular fibrillation and protection against this serious heart disease, representing a promising therapeutic target for future research.
reference:
Rafael Romero et al. “Activation of p38γ/δ alters the electrical activity of the heart and predisposes to ventricular arrhythmias.” Nature cardiovascular research (2023).