Placental Growth Factor Provides a Novel Local Angiogenic Therapy for Ischemic Cardiomyopathy

Kolakowski, Stephen; Berry, Mark F.; Atluri, Pavan; Grand, Todd; Fisher, Omar; Moise, Mireille A.; Cohen, Jeffrey Е.; Hsu, Vivian M.; Woo, Y. Joseph

doi:10.1111/j.1540-8191.2006.00296.x

Cited by 42 publications

(32 citation statements)

References 18 publications

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“…27 Kolakowski and colleagues were able to demonstrate the beneficial effects of PlGF on the infarcted heart after direct myocardial injection. 4 In the present study, similar results were obtained when comparing groups I and II in regards to LVEF, scar area, and angiogenesis analysis. Protein delivery was optimized by using the same PlGF dosage as in previous studies but with better results due to the use of nanoparticles as the drug delivery system.…”

Section: Discussionsupporting

confidence: 86%

“…One of these factors is placental growth factor (PlGF). 4 PlGF is a 50 kDa homodimeric glycoprotein sharing 53% sequence homology at the amino acid level with vascular endothelial growth factor (VEGF). PlGF is able to bind with high affinity to the fms-like tyrosine kinase (Flt-1) receptor but not to the kinase domain region receptor, thought to be critically involved in mediating VEGF biological action.…”

Section: Introductionmentioning

confidence: 99%

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Intramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model

Binsalamah¹,

Paul²,

Khan³

et al. 2011

IJN

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Background Acute myocardial ischemia results in scar formation with ventricular dilatation and eventually heart failure. Placental growth factor (PlGF) is reported to stimulate angiogenesis and improve cardiac function. In this study, it was hypothesized that intramyocardial injection of PlGF contained in nanoparticles can be released at the site of action for an extended time period as a sustained slow-release protective mechanism that accelerates myocardial recovery in a rat model of ischemic cardiomyopathy. Methods PlGF-loaded chitosan-alginate nanoparticles were injected into an acute myocardial infarction model in rats (n = 10 per group). Transthoracic echocardiography was performed at different time intervals. Enzyme-linked immunosorbent assay was used to measure the serum cytokines levels at 8 weeks. Hearts were stained with Masson’s trichrome for scar area analysis. Immunofluorostaining was performed to evaluate the extent of myocardial angiogenesis at the infarction border. PlGF enzyme-linked immunosorbent assay was used to measure the in vitro release kinetics of PlGF-loaded nanoparticles. Results At 8 weeks after coronary ligation, hearts that were treated with PlGF-loaded chitosan-alginate nanoparticles had significant increases in left-ventricular function ( P < 0.01), vascular density ( P < 0.01), and in the serum level of the anti-inflammatory cytokine interleukin-10 ( P < 0.05). There was significant decrease in scar area formation ( P < 0.05) and in serum levels of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-6 ( P < 0.01). In vitro PlGF-release kinetic studies showed a sustained release of PlGF from the particles over a 120-hour period. Conclusion The use of nanoparticles as a vehicle for PlGF delivery, as opposed to the direct injection of the growth factor after acute myocardial infarction, can provide sustained slow-release PlGF therapy, enhancing the positive effects of the growth factor in the setting of acute myocardial ischemia.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Intramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model

Binsalamah¹,

Paul²,

Khan³

et al. 2011

IJN

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“…4 Moreover, PlGF seems to have beneficial effects in a number of hypoxia-associated conditions. 6,8 PlGF À/À mice showed a more pronounced increase in VEGF protein levels in the distal colon after DSS administration compared with PlGF þ / þ mice, which was preventable by exogeneous administration of PlGF. Interestingly, this boost in VEGF was not able to compensate for the decrease in angiogenesis caused by the absence of PlGF.…”

Section: Discussionmentioning

confidence: 99%

“…PlGF has been shown to have beneficial effects in wound healing and ischemic cardiac disease. 4,7,8 The function of angiogenesis in IBD pathogenesis remains poorly understood because of its opposing effects. On one hand, angiogenesis is a crucial process to supply oxygen and nutrients to promote healing of the damaged mucosa.…”

mentioning

confidence: 99%

Absence of placental growth factor blocks dextran sodium sulfate-induced colonic mucosal angiogenesis, increases mucosal hypoxia and aggravates acute colonic injury

Hindryckx

Waeytens

Laukens

et al. 2010

Laboratory Investigation

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Angiogenesis has recently been described as a component of inflammatory bowel disease. Placental growth factor (PlGF), a vascular endothelial growth factor (VEGF) homologue, establishes its angiogenic capacity under pathophysiological conditions. We investigated the function of PlGF in experimental models of acute colitis. Acute colonic damage was induced in PlGF knock-out (-/-) mice and PlGF wild-type (+/+) mice by dextran sodium sulfate (DSS) and trinitrobenzenesulfonic acid (TNBS). The concentrations of PlGF and VEGF were measured in distal colonic lysates using an enzyme-linked immunosorbent assay. Colonic injury was evaluated by assessing colon length, colonocyte apoptosis (by terminal dUTP nick-end labeling), colonic cytokine production and histological score. Infiltration of polymorphonuclear cells was determined by assaying myeloperoxidase (MPO) activity. In a separate experiment, recombinant PlGF was administered to PlGF -/- mice by adenoviral transfer before DSS administration. Mucosal vascularization was quantified by computerized morphometric analysis of CD31-stained distal colonic sections. Colonic mucosal hypoxia was visualized by pimonidazole staining. Both VEGF and PlGF were upregulated during acute colitis. In addition, compared with PlGF +/+ controls, PlGF -/- mice showed a significant increase in weight loss and colonic shortening during both DSS and TNBS colitis. This correlated with enhanced colonocyte apoptosis, elevated colonic cytokine levels and increased histological damage score, but not with enhanced inflammatory cell infiltration (MPO activity). The increased morbidity of PlGF -/- mice during DSS colitis was preventable by adenovirus (Ad)-mediated overexpression of PlGF. After the administration of DSS, strongly reduced mucosal angiogenesis was observed in PlGF -/- mice compared with PlGF +/+ mice. This was associated with an early increase in intestinal epithelial pimonidazole accumulation in PlGF -/- mice, suggesting a function of enhanced epithelial hypoxia in the observed differences between the two groups. In summary, our data show that the absence of PlGF strongly inhibits mucosal intestinal angiogenesis in acute colitis, which is associated with an early increase in intestinal epithelial hypoxia and aggravation of the course of the disease

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“…Placental growth factor (PlGF), a homolog of VEGF, is reported to stimulate angiogenesis and arteriogenesis [9][10][11] with an efficacy at least comparable to that of VEGF, but without any of the side-effects that normally accompany VEGF therapy, such as edema, hypotension, 12 and hemangioma-genesis. We have recently demonstrated that PlGF is produced rapidly in infarcted myocardial tissue, and that the plasma level of PlGF after MI is positively correlated with the improvement in left ventricular function in patients with AMI.…”

mentioning

confidence: 99%

Treatment With Recombinant Placental Growth Factor (PlGF) Enhances Both Angiogenesis and Arteriogenesis and Improves Survival After Myocardial Infarction

Takeda

Uemura

Iwama

et al. 2009

Circ J

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Background: Placental growth factor (PlGF), a homolog of vascular endothelial growth factor, is reported to stimulate angiogenesis and arteriogenesis in pathological conditions. It was recently demonstrated that PlGF is rapidly produced in myocardial tissue during acute myocardial infarction (MI). However, the effects of exogenous PlGF administration on the healing process after MI are not fully understood. The purpose of the present study was to examine whether PlGF treatment has therapeutic potential in MI. Methods and Results: Recombinant human PlGF (rhPlGF: 10 μg) was administered continuously for 3 days in a mouse model of acute MI. rhPlGF treatment significantly improved survival rate after MI and preserved cardiac function relative to control mice. The numbers of CD31-positive cells and α-smooth muscle actin-positive vessels in the infarct area were significantly increased in the rhPlGF group. Endothelial progenitor cells (Flk-1 + Sca-1 + cells) were mobilized by rhPlGF into the peripheral circulation. Furthermore, rhPlGF promoted the recruitment of GFP-labeled bone marrow cells to the infarct area, but only a few of those migrating cells differentiated into endothelial cells. Conclusions: Exogenous PlGF plays an important role in healing processes by improving cardiac function and stimulating angiogenesis following MI. It can be considered as a new therapeutic molecule. (Circ J 2009; 73: 1674 -1682

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Placental Growth Factor Provides a Novel Local Angiogenic Therapy for Ischemic Cardiomyopathy

Cited by 42 publications

References 18 publications

Intramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model

Intramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model

Absence of placental growth factor blocks dextran sodium sulfate-induced colonic mucosal angiogenesis, increases mucosal hypoxia and aggravates acute colonic injury

Treatment With Recombinant Placental Growth Factor (PlGF) Enhances Both Angiogenesis and Arteriogenesis and Improves Survival After Myocardial Infarction

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