American journal of physiology. Heart and circulatory physiology vol:304 issue:6 pages:H885-H894
Background. Placental growth factor (PlGF) has a distinct biologic phenotype with a predominant proangiogenic role in disease without affecting quiescent vessels in healthy organs. We tested whether systemic administration of recombinant human (rh)PlGF improves regional myocardial blood flow and systolic function recovery in a porcine chronic myocardial ischemia model. Methods. We implanted a flow-limiting stent in the proximal LAD and measured systemic hemodynamics, regional myocardial function using magnetic resonance imaging, and blood flow using colored microspheres 4 weeks later. Animals were then randomized in a blinded way to receive rhPlGF infusion (15µg/kg/day, n=9) or PBS (Control, n=10) for 2 weeks. At 8 weeks, myocardial perfusion and function were re-assessed. Results. Infusion of rhPlGF transiently increased PlGF serum levels more than 30-fold (1153±180 vs 33±19 pg/ml at baseline, p<0.001) without affecting systemic hemodynamics. From 4 to 8 weeks, rhPlGF increased regional myocardial blood flow (MBF) from 0.46±0.11 to 0.85±0.16ml/min/g, with a concommitant increase in systolic wall thickening (SWT) from 11±3% to 26±5% in the ischemic area. In control animals, no significant changes from 4 to 8 weeks were observed (MBF: 0.45±0.07 to 0.49±0.08 ml/min/g and SWT: 14±4% to 18±1%). rhPlGF-induced functional improvement was accompanied by increased myocardial neovascularization, enhanced glycogen utilization, and reduced oxidative stress and cardiomyocyte apoptosis in the ischemic zone. Conclusions. Systemic rhPlGF infusion significantly enhances regional blood flow and contractile function of chronic ischemic myocardium without adverse effects. PlGF protein infusion may represent an attractive therapeutic strategy to increase myocardial perfusion and energetics in chronic ischemic cardiomyopathy.