HOUSTON (Sept. 15, 2023) — In collaboration with a team of international scientists, Xiao Li, PhD, from the Gene Editing Lab at The Texas Heart Institute^®, recently discovered a novel protective mechanism that suppresses autoimmunity and inflammation in the heart after a heart attack (also known as myocardial infarction). Naturally, this protective mechanism in the body rescues the heart from autoimmunity-mediated complications after an attack. During a heart attack, the heart muscle tissues are severely injured from a lack of blood flow and eventually die. These injuries in the heart muscles trigger an autoimmune response that further attacks heart tissues, gradually leading to heart failure. Thus, patients with autoimmune diseases are at increased risk of suffering worse outcomes from a heart attack.

This pioneering study, recently published in the prestigious Immunity journal, suggests that boosting this immunosuppressive program can ease autoimmunity-mediated heart attack complications.

 

The heart is susceptible to autoimmune attacks. Heart injury, such as from a heart attack, releases antigens, which build up autoreactive lymphocytes in an inflammatory environment in which the heart suffers further damage. The antigens released from damaged heart cells induce autoimmunity through activated dendritic cells and cardiac antigen-specific “killer T cells,” also known as cytotoxic T cells, which are the main culprits inhibiting heart repair.

 

Interestingly, heart attack-induced autoimmunity is transient and usually resolved because the heart must keep injury-induced autoimmunity in check to avoid inflammatory consequences that gradually lead to heart failure. The underlying mechanism was unknown until this groundbreaking study, showing that a protective mechanism is indeed inherently present. Dr. Li and collaborators reported that a T-box protein TBX1, known to affect the development of cardiac structure and lymphatic vessels, is responsible for diminishing the autoimmune mechanisms mediated by the cytotoxic T cells. They observed that TBX1 activates the expression of many proteins in the lymphatic vessel endothelial cells, promoting the formation of new vessels and enhancing the immunosuppressive, or anti-inflammatory, functions of these cells. Notably, TBX1 mobilizes these endothelial cells into the damaged heart regions and helps establish an immunosuppressive environment, inhibiting cytotoxic T cell and promoting macrophage expansions. This unique role of TBX1 facilitates heart repair after an injury.

 

This landmark study reveals that the autoimmune suppression program initiates and the consequent inflammation diminishes early, approximately on the fourth day of a heart attack. On the basis of their findings, Dr. Li and the scientific team rationalize a roadmap for future heart attack therapeutics. Immunosuppressive treatments at this early time after a heart attack may be efficient and will synchronize with the body’s endogenous immunosuppressive mechanism to provide a synergetic beneficial effect. Therefore, short-term immunosuppression may be sufficient in heart attack treatment, thereby avoiding the side effects of long-term immunosuppression.

 

Patients with DiGeorge syndrome (known as 22q11.2 deletion syndrome [22q11.2DS]) have the TBX1 gene deleted and are born with congenital heart disease (CHD) because of poor heart development, along with other anomalies. With the advancement in pediatric care, the adult patient population with 22q11.2DS is growing. Unfortunately, because the TBX1protein is absent in these adult CHD patients, they are at an increased risk of heart attack and mortality associated with persistent autoimmune attacks on the damaged heart. Therefore, preventive care is more vital than immunosuppressive interventions in these patients.