Platelet derived growth factor-AB modulates post-infarct myocardium leading to extended improvement in cardiac function.

Abstract

Myocardial infarction (MI) contributes to significant morbidity and mortality globally. Platelet derived growth factor-AB (PDGF-AB) is potentially a novel translational therapeutic for improving cardiac function post-MI, which we assess here using a 60 day porcine left anterior descending artery occlusion ischemia-reperfusion model. MI was induced in 10 female Landrace swine, with 5 controls, 5 receiving PDGF-AB treatment and 2 additional shams. PDGF-AB improved left ventricular ejection fraction 58 days after MI, without affecting overall infarct scar size, as shown using serial cardiac magnetic resonance imaging. Preserved infarct zone microvascular function and increased vessel maturity was also observed. Multi-omic analyses showed that PDGF-AB treatment altered the expression of proteins, metabolites, and lipids that are known to be involved in myocardial energetics and redox balance. Novel therapeutics such as PDGF-AB may lead to more sustained salvage of cardiac function by modulating the post-MI microvasculature, myocardium and extracellular matrix.