Beneficial effects of prolonged systemic administration of PIGF on late outcome of post-ischaemic myocardial performance

Recent evidence indicates that an imbalance between cardiomyocyte hypertrophy and blood vessel growth in the remote myocardium may contribute to heart failure in ischaemic heart disease. It remains, however, largely unknown which angiogenic factors are capable of stimulating vessel growth in the remote myocardium after myocardial infarction (MI) and whether systemic, rather than local, administration of such factors suffices to ameliorate post-MI cardiac recovery. We therefore analysed the effect of systemic placental growth factor (PIGF) delivery on myocardial recovery post-MI in mice. MI was induced by permanent ligation of the left anterior descending coronary (LAD) artery in C57B16/J mice, followed by systemic injection of a PIGF adenovirus, resulting in elevated circulating levels of PIGF for 4 weeks. Functional and morphological analysis revealed that PIGF treatment induced cardiomyocyte hypertrophy and improved cardiac recovery at day 28 post-MI. PIGF stimulated angiogenesis in the infarct border and vessel enlargement in the remote myocardium. In this mouse model, capillary-to-cardiomyocyte ratios in the remote myocardium were maintained post-MI, but PIGF increased the vascular perfusion area in balance with the cardiomyocyte hypertrophy. Overall, systemic delivery of PIGF improves cardiac performance and promotes adaptive remodelling of the post-MI heart. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.