Two anti-inflammatory molecules reduce the inflammatory response within the injured heart and reduce scarring, according to new research published in The American Journal of Pathology

Research into the protective effects of two anti-inflammatory molecules, transforming growth factor-beta1 (TGFβ1) and Heligmosomoides polygyrus TGM (HpTGM), following heart attack found that both proteins reduced the inflammatory response within the injured heart and reduced mature scarring. Anti-inflammatory therapy to treat patients following acute myocardial infarction is an exciting prospect that deserves further translational studies, report investigators in The American Journal of Pathology, published by Elsevier.

Patients with acute heart attacks (ST elevation myocardial infarction, or STEMI) are very likely to survive if they undergo timely reopening of the occluded coronary artery (coronary reperfusion) in specialized clinical centers. Despite the given survival rates and major improvements in treatment, progression to heart failure still represents a major clinical problem. The patients’ longer-term outcomes depend on the extent of the damage to their heart tissue.

Lead investigator Helen M. Arthur, PhD, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, explains: “Coronary reperfusion after STEMI is standard therapy to salvage ischemic heart muscle. However, evidence suggests that the subsequent inflammatory response that the body initiates to repair the damaged heart tissue can also cause further loss of viable heart muscle. The more muscle that is lost, the greater the risk of subsequent progression to heart failure. The reason for this study was to investigate the potential protective effects of TGFβ1 as a possible intervention to minimize this additional damage to the heart beyond the ischemic damage caused by the heart attack itself.”

The research team found that levels of an important anti-inflammatory protein TGFβ1 in the blood of STEMI patients 24 hours after reperfusion correlated with a reduction in infarct size after three months. To investigate this further they used an established mouse model of a heart attack to test the protective effects of TGFβ1, a protein known to be released in the body in response to tissue injury. They also studied its mimic HpTGM, a protein produced by a parasitic worm to help evade the immune response and thereby enable the worm to live within the tissue lining the gut. Intravascular delivery of either of these naturally occurring anti-inflammatory proteins reduced the injurious inflammatory response within the heart and importantly, the extent of heart injury as evidenced by reduced mature scar size.

The investigators were surprised to find almost identical beneficial effects of TGFβ1 and HpTGM treatment. Although TGFβ1 and HpTGM are evolutionarily unrelated, both these molecules interact with cells in a similar manner by activating the same signalling pathway. The dose of anti-inflammatory therapy was given at the time of reperfusion, which corresponds to a clinically useful time for a therapeutic intervention in humans.

Investigators could attribute the beneficial outcomes to the protective effect of these molecules on endothelial cells—the cells lining the blood vessels that help to regulate the exit of proinflammatory white blood cells from the circulation and enter the injured tissue. TGFβ1 has well-established anti-inflammatory properties, whereas HpTGM is a parasitomimetic with great clinical potential. Recent work in the Maizels laboratory at the University of Glasgow has also shown that delivery of HpTGM has a major anti-inflammatory effect in mouse models of colitis or airway inflammation, taking advantage of the product evolved by a parasite to quell the immune response to its presence.

Dr. Arthur concluded: “The current study shows that exogenous delivery of HpTGM at the time of coronary artery reperfusion dampens the proinflammatory response of coronary endothelial cells and reduces cardiac injury, leading to increased myocardial salvage and reduced scar size with the corollary of improved prospects for long-term cardiac function. The use of HpTGM as an anti-inflammatory therapy in treating heart attack patients is clearly an exciting prospect that requires further translational studies.”

Full bibliographic information
Published  on 04/04/2024 by Elsevier
About: “Exogenous Transforming Growth Factor-β1 and Its Helminth-Derived Mimic Attenuate the Heart’s Inflammatory Response to Ischemic Injury and Reduce Mature Scar Size,”
Authors: Rachael E. Redgrave, Esha Singh, Simon Tual-Chalot, Catherine Park, Darroch Hall, Karim Bennaceur, Danielle J. Smyth, Rick M. Maizels, Ioakim Spyridopoulos, and Helen M. Arthur
Journal: It appears in The American Journal of Pathology, volume 194, issue 4 (April 2024)