Research on the protective effects of two anti-inflammatory molecules, transforming growth factor beta1 (TGFβ1) and Heligmosomoides poligyro TGM (HpTGM), after a heart attack, found that both proteins reduced the inflammatory response within the injured heart and reduced mature scarring. Anti-inflammatory therapy to treat patients after acute myocardial infarction is an interesting prospect that deserves further translational studies, researchers report in The American Journal of Pathologypublished by Elsevier.
Patients with acute heart attacks (ST-segment 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 given survival rates and significant improvements in treatment, progression to heart failure still represents a major clinical problem. Patients’ long-term outcomes depend on the extent of damage to the heart tissue.
Principal investigator Helen M. Arthur, PhD, Institute of Biosciences, School of Medical Sciences, University of Newcastle, explains: “Coronary reperfusion after STEMI is a standard therapy to salvage ischemic heart muscle. However, evidence suggests that the subsequent inflammatory response that the body initiates to repair 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 possible 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 HpTGM mimic, a protein produced by a parasitic worm to help evade the immune response and thus allow the worm to live within the tissue lining the intestine. Intravascular administration of either of these natural anti-inflammatory proteins reduced the harmful inflammatory response within the heart and, more importantly, the extent of cardiac injury, as evidenced by the reduction in mature scar size.
The researchers were surprised to find almost identical beneficial effects of TGFβ1 and HpTGM treatment. Although TGFβ1 and HpTGM are not evolutionarily related, both molecules interact with cells in a similar way by activating the same signaling pathway. The anti-inflammatory therapy dose was administered at the time of reperfusion, which corresponds to a clinically useful time for a therapeutic intervention in humans.
Researchers could attribute the beneficial results to the protective effect of these molecules on endothelial cells, the cells that line blood vessels and help regulate the exit of pro-inflammatory white blood cells from the circulation and into injured tissue. TGFβ1 has well-established anti-inflammatory properties, while HpTGM is a parasitomimetic with great clinical potential. Recent work in the Maizels laboratory at the University of Glasgow has also shown that the administration of HpTGM has an important anti-inflammatory effect in murine models of colitis or airway inflammation, taking advantage of the product developed by a parasite to quell the immune response to Your presence.
Dr. Arthur concluded: “The current study shows that exogenous administration of HpTGM at the time of coronary artery reperfusion blunts the proinflammatory response of coronary endothelial cells and reduces cardiac injury, leading to greater cardiac rescue.” myocardium and a reduction in scar size with the corollary of better prospects “for long-term cardiac function. “The use of HpTGM as an anti-inflammatory therapy in the treatment of patients with heart attacks is clearly an interesting prospect that requires further translational studies.”