A study in which Dr. José Martínez-González, researcher at the Instituto de Investigaciones Biomédicas de Barcelona (IIBB-CSIC) and the IIB-Sant Pau, carried out at the National Cardiovascular Research Center (CNIC), reveals a key factor that protects the heart after a heart attack.
The research, led by Dra. Pilar Martín, head of the Inflammatory Processes Regulatory Molecules Group of the CNIC and published today in the Journal of Clinical Investigation, describes that the expression of the CD69 receptor in regulatory T lymphocytes confers protection after suffering a myocardial infarction, since it acts as a control point for the exacerbated inflammation responsible for heart damage in the medium term.
In addition, the work in which researchers from the Cardiovascular Diseases area of the CIBER (CIBERCV) from the group of Dr. Francisco Sánchez-Madrid at the CNIC and the La Princesa University Hospital have also participated, reveals that expression levels of this CD69 receptor in peripheral blood could predict the development of heart failure, that is, serious sequelae in the functionality of the heart.
Regulatory T lymphocytes, explains Dr. Rafael Blanco-Domínguez, first signatory of the work, “are cells in charge of controlling other elements of the immune system to prevent uncontrolled inflammatory responses from ending up causing unwanted damage”.
The researchers, through the analysis of blood immunologic markers of 283 patients with myocardial infarction, ischemic heart disease and the main cause of death in the world, have discovered that there is an increase in the expression of this receptor CD69 in regulatory T lymphocytes in the first hours after the ischemic event.
Thanks to experiments with mouse models, this team of scientists has revealed that the absence of CD69 leads to an increase in inflammation, cardiac dysfunction and the death rate after a heart attack.
This phenomenon, explains Dra. Martín, “this is because the regulatory T cells that express CD69 are recruited at the site of the infarction and are necessary to inhibit the gamma-delta T cells, which secrete the pro-inflammatory interleukin-17. The presence of CD69 makes the regulatory T cells more efficient in inducing death and inhibiting the secretion of interleukin-17 by means of a novel mechanism independent of specific antigens”.
Research has also shown that a very relevant fact: therapy with regulatory T cells that express CD69 after a heart attack in mice deficient in CD69 is sufficient to compensate for the deficiency of this molecule and thus reduce cardiac inflammation and improve survival.
The follow-up of patients with heart attacks in two independent cohorts, in close collaboration with the Cardiology Services of the University Hospital of La Princesa in Madrid and the Hospital de la Santa Creu i Sant Pau in Barcelona, revealed another very promising result for the clinic.
The levels of expression of CD69 in peripheral blood serve to predict the development of heart failure, that is to say, serious sequelae in the functionality of the heart. In other words, explains Dr. Blanco-Domínguez, those patients with low levels of CD69 in the first hours after a heart attack “had a greater risk of developing heart failure during the first two and a half years after hospital admission”.
The authors conclude that this work reveals a new regulatory mechanism of inflammation after myocardial infarction and opens the door to the development of CD69 as a prognostic and therapeutic candidate for this global cardiac affectation.
This study has had the support of the Ministry of Science and Innovation (MCIN), through the Carlos III Health Institute (ISCIII) – Health Research Fund; Scholarships Community of Madrid; Foundation La Marató TV3; CIBERFES, Human Frontier Science Program; Leducq Transatlantic Networks; Marie Skłodowska-Beca, and support from the University Teacher Training program of the Ministry of Education, Culture and Sports.
Blanco-Domínguez … José Martínez-González, Pilar Martín. CD69 expressió on regulador T cells protects from immune damage after myocardial infarction. J Clin Invest. 2022. https://doi.org/10.1172/JCI152418.
