Delivery of TGF-β1 Following Heart Attack Reduces Reperfusion Injury
A heart attack is triggered by rupture of an atherosclerotic plaque and downstream blockage of an important vessel feeding oxygenated blood to heart tissue. Much of the permanent harm resulting from a heart attack occurs when blood flow is restored to ischemic tissue, however. A cascade of maladaptive reactions, inflammation, and cell death occurs, leading to scarring and loss of function in the heart muscle. This damage to the heart can be reduced to some degree by anti-inflammatory signaling applied soon after the heart attack takes place, as researchers here demonstrate.
Despite major improvements using primary percutaneous intervention (PPCI) to treat patients with acute ST-elevation myocardial infarction (STEMI), progression to heart failure after infarction represents a major clinical problem. Despite state-of-the-art medical care, 22% of patients with STEMI treated with PPCI develop heart failure symptoms within 1 year. Detrimental progression is substantively determined by the original infarct size and time to reperfusion. An acute exuberant proinflammatory response can further enhance local cardiac injury. Over time, this can lead to adverse ventricular remodeling and gradual loss of cardiac function that can result in heart failure. For patients with STEMI, particularly those with large infarcts, additional intervention in the acute phase is needed to reduce ischemia-reperfusion injury and protect myocardial tissue, thereby reducing the risk of progression to heart failure.
Transforming growth factor (TGF)-β1 is a potent anti-inflammatory cytokine released in response to tissue injury. The aim of this study was to investigate the protective effects of TGF-β1 after myocardial infarction. In patients with STEMI, there was a significant correlation between higher circulating TGF-β1 levels at 24 hours after myocardial infarction and a reduction in infarct size after 3 months, suggesting a protective role of early increase in circulating TGF-β1. A mouse model of cardiac ischemia reperfusion was used to demonstrate multiple benefits of exogenous TGF-β1 delivered in the acute phase. It led to a significantly smaller infarct size (30% reduction), reduced inflammatory infiltrate (28% reduction), lower intracardiac expression of inflammatory cytokines IL-1β and CCL2 (more than a 50% reduction) at 24 hours, and reduced scar size at 4 weeks (21% reduction) after reperfusion.