2023-11-27 18:00:04
An investigation carried out by the teams of Guadalupe Sabio y Jose Jalife at the National Cardiovascular Research Center of Madrid (CNIC) has discovered a new signaling pathway that would be behind the appearance of ventricular fibrillation, a type of cardiac arrhythmia. The work, which has just been published in the magazine Nature Cardiovascular Research offers new hope for tackling this potentially deadly condition.
Ventricular fibrillation is the main immediate cause of sudden cardiac death. Although aging is one of the best-established risk factors for the development of cardiac arrhythmias, the mechanisms behind this connection have been elusive, hampering the development of cardiac arrhythmias. specific treatment development.
Ventricular fibrillation is the main immediate cause of sudden cardiac death
The heart beats in a regular and coordinated manner to efficiently pump blood through the body. To do this, it has to coordinate the contraction of all its cells and each heartbeat has to follow a meticulously orchestrated pattern. When an arrhythmia appears, the heart rhythm is altered, accelerates, becomes irregular and is potentially fatal.
Optical mapping images of two different hearts from mice that developed ventricular fibrillation. / CNIC
Studying rodent modelsCNIC researchers discovered the relationship between the stress protein kinases p38γ and p38δ and the development of ventricular fibrillation, regardless of sex.
This discovery opens new avenues for possible therapeutic interventions for this pathology.
Critical role in the development of arrhythmias
The researchers observed that the activation of p38γ and p38δ increased in the hearts of aged mices and those with genetic or drug-induced conditions predisposing to arrhythmias, suggesting that this pathway played a critical role in the development of this condition.
The authors discovered the relationship between the stress protein kinases p38γ and p38δ and the development of ventricular fibrillation, regardless of sex
According to Rafael Romerofirst signatory of the article and CNIC researcher, “when we realized that the activation of these p38 was common in different arrhythmogenic situations, we knew that they could play a key role that needed to be investigated.”
The exhaustive study of this signaling pathway revealed that, when these protein kinases are activated, they alter the electrical properties of cardiomyocytes, leading to the appearance of arrhythmias. This happens due to the alteration of existing ion channels in the heart muscle cells responsible for coordinating cell contraction.
When these protein kinases are activated, they alter the electrical properties of cardiomyocytes, leading to the appearance of arrhythmias.
The researchers found that p38γ and p38δ phosphorylate the ryanodine receptor 2 (RyR2) and the SAP97 protein, disturbing the localization of the Kv4.3 channel. presenting them as new substrates of p38γ and p38δ. Ultimately, these molecular changes resulted in the appearance of premature ventricular activity and increased susceptibility to ventricular fibrillation.
These findings could open new perspectives for the preversal of sustained ventricular fibrillation and protection against this serious heart condition, offering a promising therapeutic target for future research.
Reference:
Rafael Romero et al. “p38γ/δ activation alters cardiac electrical activity and predisposes to ventricular arrhythmia”. Nature Cardiovascular Research (2023).
Rights: Creative Commons.
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