PlGF: A Multitasking Cytokine with Disease-Restricted Activity

Dewerchin, Mieke; Carmeliet, Peter

doi:10.1101/cshperspect.a011056

Cited by 188 publications

(181 citation statements)

References 181 publications

(253 reference statements)

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“…ANG‐2 and PLGF were found to be the most abundantly secreted angiogenic growth factors, independent of underlying ischemic disease. Both ANG‐2 and PLGF play an important role in the complex cytokine cocktail, mediating the overall neovascularization process in ischemic disease 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47…”

Section: Discussionmentioning

confidence: 99%

Neovascularization Potential of Blood Outgrowth Endothelial Cells From Patients With Stable Ischemic Heart Failure Is Preserved

Dauwe

Pelacho

Wibowo

et al. 2016

JAHA

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BackgroundBlood outgrowth endothelial cells (BOECs) mediate therapeutic neovascularization in experimental models, but outgrowth characteristics and functionality of BOECs from patients with ischemic cardiomyopathy (ICMP) are unknown. We compared outgrowth efficiency and in vitro and in vivo functionality of BOECs derived from ICMP with BOECs from age‐matched (ACON) and healthy young (CON) controls.Methods and ResultsWe isolated 3.6±0.6 BOEC colonies/100×106 mononuclear cells (MNCs) from 60‐mL blood samples of ICMP patients (n=45; age: 66±1 years; LVEF: 31±2%) versus 3.5±0.9 colonies/100×106 MNCs in ACON (n=32; age: 60±1 years) and 2.6±0.4 colonies/100×106 MNCs in CON (n=55; age: 34±1 years), P=0.29. Endothelial lineage (VEGFR2+/CD31+/CD146+) and progenitor (CD34+/CD133−) marker expression was comparable in ICMP and CON. Growth kinetics were similar between groups (P=0.38) and not affected by left ventricular systolic dysfunction, maladaptive remodeling, or presence of cardiovascular risk factors in ICMP patients. In vitro neovascularization potential, assessed by network remodeling on Matrigel and three‐dimensional spheroid sprouting, did not differ in ICMP from (A)CON. Secretome analysis showed a marked proangiogenic profile, with highest release of angiopoietin‐2 (1.4±0.3×105 pg/106 ICMP‐BOECs) and placental growth factor (5.8±1.5×103 pg/106 ICMP BOECs), independent of age or ischemic disease. Senescence‐associated β‐galactosidase staining showed comparable senescence in BOECs from ICMP (5.8±2.1%; n=17), ACON (3.9±1.1%; n=7), and CON (9.0±2.8%; n=13), P=0.19. High‐resolution microcomputed tomography analysis in the ischemic hindlimb of nude mice confirmed increased arteriogenesis in the thigh region after intramuscular injections of BOECs from ICMP (P=0.025; n=8) and CON (P=0.048; n=5) over vehicle control (n=8), both to a similar extent (P=0.831).Conclusions BOECs can be successfully culture‐expanded from patients with ICMP. In contrast to impaired functionality of ICMP‐derived bone marrow MNCs, BOECs retain a robust proangiogenic profile, both in vitro and in vivo, with therapeutic potential for targeting ischemic disease.

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Section: Discussionmentioning

confidence: 99%

Neovascularization Potential of Blood Outgrowth Endothelial Cells From Patients With Stable Ischemic Heart Failure Is Preserved

Dauwe

Pelacho

Wibowo

et al. 2016

JAHA

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“…Recent studies have implied that PlGF-2 is a multitasking cytokine that stimulates and activates numerous cell types, including bone marrow-derived cells. 14,[19][20][21] Apart from its traditional role as an angiogenic GF, PlGF-2 also plays an important role in bone remodeling and regeneration. 10,18 Blocking of PlGF-2 receptors could inhibit bone formation in vivo.…”

Section: Introductionmentioning

confidence: 99%

“…17 However, the current research suggests that PlGF-2 could be expressed by a series of cell types, including progenitors of the bone marrow. 6,[18][19][20] Maes et al 18 indicated that the expression of PlGF-2 and its receptor increased throughout the repair process, and they suggested that PlGF-2 coordinates the key aspects of bone repair. Moreover, PlGF-2 receptors, including neuropilin-2, are also expressed in osteoblast lineage cells during the repair of fractures, indicating a potent "switch" role of PlGF-2 in the process of osteogenesis.…”

mentioning

confidence: 99%

“…19 The key role of PlGF-2 in the osteogenesis/angiogenesis crosstalking framework could also be explained by its predominant role as the angiogenic and inflammatory "switch". 19,20,53 Considering that the bone remodeling process is mediated by a series of inflammatory factors, it is reasonable to believe that PlGF-2 may play a key role in the osteogenesis/angiogenesis crosstalking framework. It can be concluded that there is an as yet unidentified molecular framework coupling osteogenesis and angiogenesis, and PlGF-2 plays key roles in such a framework.…”

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confidence: 99%

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Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis

Liu

Deng

Sun

et al. 2016

IJN

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Objective To compare the direct osteogenic effect between placental growth factor-2 (PlGF-2) and bone morphogenic protein-2 (BMP-2). Methods Three groups of PlGF-2/BMP-2-loaded heparin– N -(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) nanocomplexes were prepared: those with 0.5 μg PlGF-2; with 1.0 μg BMP-2; and with 0.5 μg PlGF-2 combined with 1.0 μg BMP-2. The loading efficiencies and release profiles of these growth factors (GFs) in this nanocomplex system were quantified using enzyme-linked immunosorbent assay, their biological activities were evaluated using cell counting kit-8, cell morphology, and cell number counting assays, and their osteogenic activities were quantified using alkaline phosphatase and Alizarin Red S staining assays. Results The loading efficiencies were more than 99% for the nanocomplexes loaded with just PlGF-2 and for those loaded with both PlGF-2 and BMP-2. For the nanocomplex loaded with just BMP-2, the loading efficiency was more than 97%. About 83%–84% of PlGF-2 and 89%–91% of BMP-2 were stably retained on the nanocomplexes for at least 21 days. In in vitro biological assays, PlGF-2 exhibited osteogenic effects comparable to those of BMP-2 despite its dose in the experiments being lower than that of BMP-2. Moreover, the results implied that heparin-based nanocomplexes encapsulating two GFs have enhanced potential in the enhancement of osteoblast function. Conclusion PlGF-2-loaded heparin–HTCC nanocomplexes may constitute a promising system for bone regeneration. Moreover, the dual delivery of PlGF-2 and BMP-2 appears to have greater potential in bone tissue regeneration than the delivery of either GFs alone.

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“…Unlike VEGF, PlGF has diverse roles in tissue ischemia, malignancy, inflammation, and several other diseases. 13 Placental protein 13 (PP 13) is one of the several placental proteins of importance in many biochemical and physiological effects in the trophoblast membrane related to implantation, blood pressure regulation, and tissue oxygenation. Little is known of its effects not directly related to pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Placental growth factor and placental protein 13 in patients with Balkan endemic nephropathy, a worldwide disease

et al. 2015

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PlGF: A Multitasking Cytokine with Disease-Restricted Activity

Cited by 188 publications

References 181 publications

Neovascularization Potential of Blood Outgrowth Endothelial Cells From Patients With Stable Ischemic Heart Failure Is Preserved

Neovascularization Potential of Blood Outgrowth Endothelial Cells From Patients With Stable Ischemic Heart Failure Is Preserved

Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis

Placental growth factor and placental protein 13 in patients with Balkan endemic nephropathy, a worldwide disease

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