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


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).


CONCLUSIONS
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.
Department of Cardiology.
Liyun
L
Luo
Department of Cardiology.
Bairong
B
Chen
Department of Cardiology.
Yin
Y
Huang
Department of Oncological Radiotherapy, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, People's Republic of China.
Zibin
Z
Liang
Department of Cardiology.
Songbiao
S
Li
Department of Cardiology.
Yuelan
Y
Yin
Department of Cardiology.
Jian
J
Chen
Department of Cardiology.
Wei
W
Wu
D000818:Animals; D001120:Arginine / Q000008:administration & dosage* / Q000378:metabolism; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D006352:Heart Ventricles / Q000737:chemistry* / Q000378:metabolism; D009203:Myocardial Infarction / Q000503:physiopathology; D000072483:Placenta Growth Factor / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects*
D000072483:Placenta Growth Factor; D001120:Arginine
acute myocardial infarction; angiogenesis; l-arginine; placental growth factor