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

Abstract

ObjectiveExogenous 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 methodsFifty 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.ResultsLeft 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).ConclusionExogenous 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.

Treatment with placental growth factor attenuates myocardial ischemia/reperfusion injury

“…Earlier experimental studies have shown that the activation of VEGFR1 by PlGF could improve cardiac function and survival rate in animal models experiencing heart failure by enhancing angiogenesis and arteriogenesis. [ 10 , 23 – 25 ] The angiogenic growth factor, PlGF, was also reported to be involved in the growth and spread of cancer and that PlGF and Flt-1 were expressed in 36% to 60% and 65% of primary breast cancers respectively, which suggested that PlGF may also be active in cell growth and metastasis. [ 26 ] In addition, the administration of PlGF after AMI induced not only enlargement of vessel size, but also compensatory hypertrophy of cardiomyocyte in remote non-infarcted myocardium.…”

Proteomic profiling for detection of early‐stage heart failure in the community

“…The observed increase in PGF might indicate its involvement already in early stages of cardiac remodelling and dysfunction in response to pressure overload and ischaemia. In experimental setting, administration of exogenous PGF after acute myocardial infarction stimulates angiogenesis and improves ventricular remodelling and function 27 . Similarly, endogenous PGF was required for adaptive angiogenesis and HF prevention by inducing cardiac hypertrophy after pressure overload in mice 28 …”

“…In experimental setting, administration of exogenous PGF after acute myocardial infarction stimulates angiogenesis and improves ventricular remodelling and function. 27 Similarly, endogenous PGF was required for adaptive angiogenesis and HF prevention by inducing cardiac hypertrophy after pressure overload in mice. 28 Galectin-9 belongs to a family of carbohydrate-binding proteins and is produced by the extracellular matrix.…”

Improvement of cardiac dysfunction by L-arginine combined with vitamin C through restoring angiogenesis associated with NADPH/NOS/NO signal pathway in diabetic rats

“…1. Previous evidence has revealed that the single administration of L-arginine [25] or Vitamin C [27] exquisitely enhances vascularity in ischemic hearts, acting as a protective role on cardiovascular diseases, respectively. Thus, we hypothesized that the combination therapy of L-arginine and vitamin C is a promising therapeutic option that plays a better myocardial protection effect than single use hyperglycemia-impaired angiogenic response in diabetic AMI.…”

“…For example, L-arginine administration presumably caused additional effects on exercise-induced angiogenesis by promoting VEGF expression in the left ventricle in middle-aged rats [43]. Placental growth factor (PlGF) and L-arginine have a more pronounced and synergistic protective effect on myocardial protection in a rat model of acute myocardial infarction [25]. L-arginine supplementation to FGF-2 therapy had myocardial microvascular reactivity and perfusion in a porcine model of endothelial dysfunction [46].…”