Exogenous TGFβ1 and its mimic HpTGM attenuate the heart's inflammatory response to ischaemic injury and improve long term cardiac outcomes

Patients with successful coronary reperfusion following acute ST-elevation myocardial infarction (STEMI) retain risk of progression to heart failure. Robust interventions are required in the acute MI setting to minimise cardiac injury and reduce risk of further detrimental progression. TGFβ1 is a cytokine released in response to infection or tissue injury. It is found at increased levels in the blood of STEMI patients immediately following myocardial infarction. We observe a significant negative correlation (p=0.003) between higher circulating TGFβ1 levels at 24h post MI and detrimental increase in infarct size over the following 3 months, suggesting that an early increase in circulating TGFβ1 is protective in these patients. Using a mouse model of cardiac ischaemia-reperfusion we demonstrate that additional exogenous TGFβ1 delivered in the acute setting has multiple beneficial outcomes. It leads to smaller infarct size, reduced inflammatory infiltrate, lower intra-cardiac expression of inflammatory cytokines IL1b and CCL2 (all at 24h post reperfusion) and reduced scar size at 4 weeks. HpTGM, a recently described low-fibrogenic mimic of TGFβ1, secreted by a helminth parasite to evade immune rejection, has a very similar protective effect on injured mouse hearts. This work reveals the potential of exogenous TGFβ1 and HpTGM to provide protective anti-inflammatory effects and reduced heart injury in the acute MI setting, leading to a smaller scar and reduced risk of heart failure ### Competing Interest Statement The authors have declared no competing interest.