New link between inflammation and pathological cardiovascular remodeling

Scientists have described a previously unknown mechanism that allows the immune-inflammatory response to contribute to the pathological remodeling of arteries in various cardiovascular diseases.

The new research provides new and revealing data on one of the mechanisms that connect the immune-inflammatory response with vascular disease, by describing the key role played by the early activation antigen of CD69 lymphocytes. The study, the result of the collaboration of scientists from the Barcelona Institute for Biomedical Research (IIBB), the Center for Biomedical Research in the Cardiovascular Disease Network (CIBERCV), the Autonomous University of Madrid (UAM) and the National Center for Cardiovascular Research ( CNIC), in Spain, paves the way for new therapeutic strategies.

Early lymphocyte activation antigen CD69 is a receptor that is induced upon stimulation of leukocytes. “Initial in vitro studies on this molecule suggested its proinflammatory role. However, there is growing in vivo evidence that highlights its role as a molecular brake to control exacerbated inflammatory responses”, explains Francisco Sánchez Madrid, head of the Intercellular Communication in Inflammatory Response group at the CNIC, group leader of the CIBERCV and one of the coordinators of this new work.

Previous research by these teams identified the role of CD69 as a receptor for oxidized low-density lipoproteins (oxLDL) on human T-lymphocytes (a type of immune cell), a binding that leads to an anti-inflammatory response that protects against atherosclerosis. Based on this work, in this new study they focused on looking for its possible role in the mechanisms that control the inflammatory-immune response and its link with tissue remodeling in cardiovascular diseases.

Using large-scale RNA expression analysis, “binding of CD69 to oxidized LDL was found to induce the expression of PD-1 (a protein found on T lymphocytes that contributes to the control of immune responses) and that this mechanism participates in the regulation of the inflammatory response”, comments María Jiménez Fernández, co-author of the study.

Members of the research team. (Photos: CNIC)

“This CD69-mediated PD-1 induction mechanism would contribute to modulating inflammation and the cardiovascular remodeling that occurs as a consequence of it,” explain Francisco Sánchez Madrid and José Martínez González, group leaders of the CIBERCV at the UAM and the IIBB, respectively, and coordinators of this new work.

“The discovery of this regulation underlines the relevant role of these molecules in inflammatory cardiovascular diseases and provides new evidence for the development of therapeutic strategies for these pathologies”, they conclude.

The study is titled “CD69-oxLDL ligand engagement induces Programmed Cell Death 1 (PD-1) expression in human CD4 + T lymphocytes”. And it has been published in the academic journal Cellular and Molecular Life Sciences. (Source: CNIC)