Research into the protective effects of two anti-inflammatory molecules, transforming growth factor-beta1 (TGFβ1) and Heligmosomoides polygyrus TGM (HpTGM), following heart attack has shown promising results. Both proteins were found to reduce the inflammatory response within the injured heart and decrease mature scarring. This study, published in The American Journal of Pathology, highlights the potential for anti-inflammatory therapy to treat patients following acute myocardial infarction, which could significantly improve outcomes for these individuals. Timely reopening of the occluded coronary artery is a standard therapy for patients with acute heart attacks (ST elevation myocardial infarction, or STEMI), but the subsequent inflammatory response can cause further damage to the heart tissue, leading to an increased risk of heart failure.
Lead investigator Helen M. Arthur, PhD, from Newcastle University, explains that while coronary reperfusion after STEMI is crucial for salvaging ischemic heart muscle, the inflammatory response that follows can contribute to the loss of viable heart tissue. The extent of this damage directly impacts the longer-term outcomes for patients, making it important to investigate potential interventions to minimize additional harm. The study found that levels of TGFβ1 in the blood of STEMI patients following reperfusion correlated with a reduction in infarct size after three months. This led researchers to explore the protective effects of TGFβ1, as well as its mimic HpTGM, in a mouse model of a heart attack.
Surprisingly, both TGFβ1 and HpTGM demonstrated almost identical beneficial effects in reducing the inflammatory response and limiting heart injury in the mouse model. Despite being evolutionarily unrelated, both molecules activate the same signalling pathway and interact with cells in a similar manner. The therapeutic dose was administered at the time of reperfusion, which is a clinically relevant time for intervention in humans. The researchers attribute the positive outcomes to the protective effect of these molecules on endothelial cells, which regulate the movement of proinflammatory white blood cells from the circulation into the injured tissue.
The study highlights the potential of using HpTGM as an anti-inflammatory therapy in treating heart attack patients. The delivery of HpTGM at the time of coronary artery reperfusion was shown to dampen the proinflammatory response of coronary endothelial cells, reducing cardiac injury, increasing myocardial salvage, and decreasing scar size. This could ultimately lead to improved long-term cardiac function for patients. HpTGM, a parasitomimetic with great clinical potential, could offer a new approach to managing the inflammatory response following acute myocardial infarction. Further translational studies are needed to explore the full potential of HpTGM as a therapeutic intervention for heart attack patients.
