Cardioprotective activity of placental growth factor combined with oral supplementation of L-arginine in a rat model of acute myocardial infarction

• Main Authors: Luo L, Chen B, Huang Y, Liang Z, Li S, Yin Y, Chen J, Wu W
• Format: Article
• Language: English
• Published: Dove Medical Press 2016-10-01
• Series: Drug Design, Development and Therapy
• Subjects: placental growth factor; L-arginine; acute myocardial infarction; angiogenesis
• Online Access: https://www.dovepress.com/cardioprotective-activity-of-placental-growth-factor-combined-with-ora-peer-reviewed-article-DDDT

Liyun Luo,1,* Bairong Chen,1,* Yin Huang,1 Zibin Liang,2 Songbiao Li,1 Yuelan Yin,1 Jian Chen,1 Wei Wu1 1Department of Cardiology, 2Department of Oncological Radiotherapy, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China*These authors contributed equally to this workObjective: Exogenous administration of placental growth factor (PlGF) stimulates angiogenesis and improves ventricular remodeling after acute myocardial infarction (AMI), and supplementation with L-arginine ameliorates endothelial function. The objective of the present study was to compare the cardioprotective effects of combination therapy of PlGF and L-arginine with those of direct administration of PlGF alone in a rat model of AMI.Materials and methods: Fifty male Sprague Dawley rats were randomly divided into five groups: sham group, normal saline group, L-arginine group, PlGF group, and combination group (PlGF + L-arginine). An AMI rat model was established by ligation of the left anterior descending of coronary arteries. After 4 weeks of postligation treatment, cardiac function, scar area, angiogenesis and arteriogenesis, myocardial endothelial nitric oxide synthase (eNOS) and collagen I protein content, and plasma concentration of brain natriuretic peptide (BNP) were studied. Echocardiography, Masson’s staining, immunohistochemical analyses, Western blot, and enzyme-linked immunosorbent assay were performed.Results: Left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), and capillary and arteriole densities were higher in the PlGF group than in the normal saline group (P<0.01). Scar area, collagen I protein content, and plasma concentration of BNP were decreased in the PlGF group (P<0.01). Myocardial eNOS protein level was elevated in the L-arginine group and PlGF + L-arginine group (P<0.01). Compared with the PlGF group, LVEF, LVFS, myocardial eNOS, and capillary and arteriole densities were higher in the combination group (P<0.01). Scar area, content of collagen I protein, and plasma concentration of BNP were reduced in the combination group (P<0.01).Conclusion: Exogenous administration of PlGF stimulates angiogenesis and improves cardiac function. L-arginine increases the expression of the eNOS protein. PlGF and L-arginine have a more pronounced, synergistic protective effect on myocardial protection compared with that of exogenous PlGF therapy alone. Keywords: placental growth factor, L-arginine, acute myocardial infarction, angiogenesis