Exogenous TGF β1 and its mimic HpTGM attenuate the heart's inflammatory response to ischaemic injury and reduce mature scar size

Am J Pathol. 2023 Oct 11:S0002-9440(23)00376-0. doi: 10.1016/j.ajpath.2023.09.014. Online ahead of print.ABSTRACTSuccessful and timely coronary reperfusion following acute ST-elevation myocardial infarction (STEMI) is standard therapy to salvage ischaemic heart muscle. However, subsequent inflammatory responses within the infarct leads to further loss of viable myocardium. TGFβ1 is a potent anti-inflammatory cytokine released endogenously in response to infection or tissue injury and the goal of this study was to investigate its protective effects when given exogenously following MI. In STEMI patients, we observe a significant correlation (p=0.003) between higher circulating TGFβ1 levels at 24h post MI and a reduction in infarct size over the following 3 months, suggesting an early increase in circulating TGFβ1 is protective. Using a mouse model of cardiac ischaemia-reperfusion we demonstrate that exogenous TGFβ1 delivered in the acute setting has multiple benefits. At 24 hours post-reperfusion it leads to a significantly smaller infarct size (30% reduction, p=0.025), reduced inflammatory infiltrate (28% reduction, p=0.015), lower intra-cardiac expression of inflammatory cytokines IL1β and CCL2 (>50% reduction, p=0.038 and 0.0004, respectively) and reduced scar size at 4 weeks (21% reduction, p=0.015). Furthermore, delivery of an equivalent dose of HpTGM, a low-fibrogenic mimic of TGFβ1, secreted by a helminth parasite to evade immune rejection, has an almost identic...
Source: Am J Pathol - Category: Pathology Authors: Source Type: research