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

• Published in: The Journal of pathology Vol. 216; no. 2; pp. 236 - 244
• Main Authors: Roncal, C, Buysschaert, I, Chorianopoulos, EK, Georgiadou, M, Meilhac, O, Demol, M, Michel, J.B, Vinckier, S, Moons, L, Carmeliet, P
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.10.2008
• Subjects: adenoviral gene transfer; Adenoviridae - genetics; Analysis of Variance; angiogenesis; Animals; Coronary Vessels - pathology; Echocardiography; Female; Genetic Therapy - methods; hypertrophy; Ligation; Mice; Mice, Inbred C57BL; Models, Animal; myocardial infarction; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardium - metabolism; Myocardium - pathology; Placenta Growth Factor; PlGF; Pregnancy Proteins - genetics; Time; Transduction, Genetic - methods
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.2408

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 (PlGF) delivery on myocardial recovery post-MI in mice. MI was induced by permanent ligation of the left anterior descending coronary (LAD) artery in C57Bl6/J mice, followed by systemic injection of a PlGF adenovirus, resulting in elevated circulating levels of PlGF for 4 weeks. Functional and morphological analysis revealed that PlGF treatment induced cardiomyocyte hypertrophy and improved cardiac recovery at day 28 post-MI. PlGF 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 PlGF increased the vascular perfusion area in balance with the cardiomyocyte hypertrophy. Overall, systemic delivery of PlGF improves cardiac performance and promotes adaptive remodelling of the post-MI heart. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.