Investigation Of PDGF-AB-and BDNF-mediated Therapeutic Angiogenesis For Ischemic Myocardium After Myocardial Infarction

Objectives:Platelet-derived growth factor-AB (PDGF-AB) is an important angiogenic factor. Previous studies mainly focus on administration of PDGF-AB or its encoded gene vector before or right after ischemia of myocardium. Recent studies indicated that Brain-derived neurotrophic factor (BDNF) is not only involved in neural development and neuron proliferation, but also involved in angiogenesis in damaged tissues. However, the investigation of PDGF-AB-and BDNF-induced therapeutic angiogenesis for ischemic myocardium after myocardial infarction is not yet reported. This study is therefore designed to investigate the effect of PDGF-AB, BDNF and their combination respectively on myocardium angiogenesis in 30 min after myocardial infarction.Methods:To study the potential therapeutic effects of PDGF-AB, BDNF and their combination after myocardial infarction, a rat myocardial infarction model was established via left anterior descending coronary artery (LAD) ligation. Histology staining (H&E and Masson's Trichrome staining) and immunohistochemistry were applied to analyze myocardial infarction size, the geometry of left ventricle (LV) and the vessel density respectively. Six groups which received different interventions respectively in 30 min after LAD ligation were set in present study. They were intramyocardial injection of 50μl PBS, intramyocardial injection of 200ng PDGF-AB, intramyocardial injection of 100ng BDNF, intramyocardial injection of 200ng PDGF-AB plus 100ng BDNF, intramyocardial injection of 100ng BDNF in 24 hours after 200ng PDGF-AB intramyocardial injection (PDGF-24H-BDNF group) and intramyocardial injection of 200ng PDGF-AB in 24 hours after 100ng BDNF intramyocardial injection (BDNF-24H-PDGF group). Results:①The infarction size (LV%) of PDGF-AB group (0.239±0.032 in female; 0.297±0.031 in male), PDGF+BDNF group (0.248±0.022 in female; 0.246±0.034 in male) and PDGF-24H-BDNF group (0.252±0.052 in female; 0.273±0.038 in male) was less than control group (0.358±0.053 in female; 0.416±0.105 in male) in two weeks after injection, and the difference had statistics significance (P<0.05). The infarction size of BDNF group (0.340±0.066 in female; 0.298±0.069 in male) and BDNF-24H-PDGF group (0.338±0.031 in female; 0.389±0.051 in male) was less than control group, but the difference had no statistics significance (P>0.05).②It was found that the wall thickness of infarcted myocardium in left ventricle (LV) of PDGF+BDNF group (0.88±0.12 mm in female) and PDGF-24H-BDNF group (0.85±0.12 mm in female) was longer than control (0.63±0.16 mm in female; 0.65±0.14 mm in male), and the difference had statistics significance (P<0.05). The thickness of infarcted myocardium in LV of PDGF-AB group (0.93±0.31 mm in female; 0.72±0.07 mm in male), BDNF group (0.77±0.17 mm in female; 0.77±0.16 mm in male), PDGF+BDNF (1.19±0.63 mm in male), PDGF-24H-BDNF (0.83±0.10 mm in male) and BDNF-24H-PDGF group (0.73±0.12 mm in female; 0.77±0.07 mm in male) was similar to the control group, and the difference had no statistics significance (P>0.05).③It was found that the wall thickness of border zone in left ventricle of PDGF-AB group (2.02±0.36 mm in female), PDGF+BDNF group (2.31±0.34 mm in female; 2.65±0.37 mm in male), PDGF-24H-BDNF group (2.25±0.28 mm in female; 2.51±0.14 mm in male), BDNF-24H-PDGF group (2.07±0.19 mm in female) was longer than control (1.69±0.24 mm in female; 1.72±0.32 mm in male), and the difference had statistics significance (P<0.05). The thickness of border zone in LV of PDGF-AB group (1.86±0.13 mm in male), BDNF group (1.79±0.22 mm in female; 2.08±0.24 mm in male) and BDNF-24H-PDGF group (2.06±0.21 mm in male) was similar to the control group, and the difference had no statistics significance (P>0.05).④The vessel density of infarcted zone of PDGF-AB group (99±7/mm2 in female) and PDGF+BDNF group (73±11/mm2 in male) was significant higher than that of the control group (63±16/mm2 in female; 54112/mm2 in male; P< 0.05). However, the difference which the PDGF-AB group (69±12/mm2 in male), BDNF (73±16/mm2 in female; 56±6/mm2 in male), PDGF+BDNF (65±13/mm2 in female), PDGF-24H-BDNF (81±19/mm2in female; 63±14/mm2 in male), BDNF-24H-PDGF (69±8/mm2 in female; 64±16/mm2 in male) was compared with control group respectively had no statistic significance (P>0.05).⑤The vessel density of border zone of PDGF-AB group (55±6/mm2 in female; 51±6/mm2 in male), BDNF group (46±5/mm2 in female), PDGF+BDNF group (55±9/mm2 in male) and BDNF-24H-PDGF group (48±6/mm2 in female; 48±3/mm2 in male) was significant higher than that of control group (38±3/mm2 in female; 40±6/mm2 in male; P<0.05). While the difference which BDNF (42±4/mm2 in male), PDGF+BDNF (40±3/mm2 in female) and PDGF-24H-BDNF (43±6/mm2 in female; 44±5/mm2 in male) was compared with control group respectively had no statistic significance (P>0.05).Conclusions:①Intramyocardial delivery of PDGF-AB in female and male rats after myocardial infarction both decrease the infarction size of ischemic myocardium, improve the reconstruction of LV geometry and increase the vessel density;②Intramyocardial delivery of BDNF in female and male rats is able to promote angiogenesis of infarcted and border zone, but the effect fail to decrease infracted size of ischemic myocardium;③The effect of PDGF-AB-mediated therapeutic angiogenesis for ischemic myocardium after myocardial infarction is better than that of BDNF;④The synergistic effect of PDGF-AB-and BDNF-mediated therapeutic angiogenesis is similar to PDGF-AB alone, however, it is better than BDNF applied alone;⑤For the time point of treatment, the effect of PDGF-24H-BDNF-mediated therapeutic angiogenesis for ischemic myocardium is similar to PDGF-AB applied alone, while it is better than BDNF applied alone and BDNF-24H-PDGF group.