Platelet-derived Growth Factor PDGF-BB Research Articles

Evaluation of mediators of fibrosis and angiogenesis in the blood serum of premature infants with bronchopulmonary dysplasia

In premature birth and postpartum damage to the developing lung, the processes of the formation of pulmonary vessels and alveoli are disrupted, leading to bronchopulmonary dysplasia (BPD). BPD is a multifactorial disease and the pathogenesis of lung tissue damage is still not fully understood. Studies of angiogenesis biomarkers can be informative for assessing the development of BPD. In this study we examined the blood serum of 65 premature infants aged 6 to 180 days of life; gestational age at birth was 23-33 weeks, body weight 480-1840 g, APGAR score 5-6. All children in the early neonatal period had respiratory distress syndrome, then 46 children formed and 19 did not form bronchopulmonary dysplasia. The concentration of the factors of angiogenesis and fibrosis was determined in blood serum by ELISA. There were no differences in the levels of angiopoietins 1 and 2, vascular endothelial growth factor VEGF-D, transforming growth factor beta TGF-β, thrombospondin-1. We observed a tendency to increasing the level of VEGF-A, which is a key regulator of angiogenesis and lung maturation; we regard this tendency as a favorable sign of lung formation. We found tendencies to increase of the adhesion molecule of endothelial platelet cells PECAM-1, interleukin 8 and connective tissue growth factor CTGF. CTGF expression is enhanced by artificial lung ventilation and exposure to high oxygen concentrations. We consider an increase of CTGF in BPD to be an unfavorable change, since the binding of CTGF to VEGF inhibits VEGF-induced angiogenesis. In children with BPD, we found a decrease in the level of platelet derived growth factor PDGF-BB, the median concentration was 3180 pg/mL in BPD versus 4782 pg/mL without BPD (p = 0.024). PDGF is an important factor in tissue regeneration and plays an important role in the formation of blood vessels. We assume the decreasing of PDGF concentration in BPD can lead to a violation of the alveolarization necessary for the formation of the structure of healthy lungs. Studies of angiogenesis factors will help to better understand the pathogenesis of lung damage in BPD.

The level of markers of apoptosis and cell proliferation in the area of restenosis after lower extremity arterial reconstruction

Aim. To assess the number of markers of apoptosis and cell proliferation, as well as their relationships in the area of restenosis of arterial reconstructions.
 Methods. The study included 14 patients with a diagnosis of arteriosclerosis obliterans of the lower extremities. Post-thrombotic occlusion of femoropopliteal bypass. All patients were males with stage III disease according to the Fontaine classification modified by A.V. Pokrovsky. The average age of the patients was 653.4 years. The mean disease duration was 92.5 months after the initial intervention. Intraoperative material distal anastomosis of femoropopliteal bypass was taken from patients during arterial reconstructions. As a control, we used arterial wall samples obtained at organ procurement from postmortem donors without arteriosclerosis obliterans of the lower extremities. The number of samples is 8. The site of their collection is the popliteal artery. After sampling, they were crushed, and a homogenate was prepared, followed by the determination of the amount of p53, PDGF BB, Bcl2, and Bax proteins using the enzyme immunoassay. Statistical analysis was performed using the Statistica 10.0 software. Group differences were assessed by using the MannWhitney test. Correlation coefficients were determined using the Spearman test. Data are presented as medians and interquartile ranges.
 Results. In tissue samples of restenosis, the amount of p53 protein was 0.07 units/mg and was significantly reduced compared with the control samples 0.14 units/mg (р=0,015). The amount of platelet-derived growth factor PDGF BB was 0.17 ng/mg (р=0.05), Bcl2 1.61 ng/mg (р=0.008), Bax 6.0 ng/mg (р=0.25) in the restenosis area and was increased in comparison with the control samples (0.04 ng/mg, 0.9 ng/mg, 4.4 ng/mg, respectively). A relationship between p53 and platelet-derived growth factor BB (r=0.724, p=0.002), platelet-derived growth factor BB and Bcl2 (r=0.672, p=0.003) was revealed in samples from restenosis tissue obtained during arterial reconstructions.
 Conclusion. The decreased apoptosis, expressed in a low level of p53 protein, with an increased Bax/Bcl-2 ratio is associated with an increase in the proliferative response of vascular wall cells in the area of restenosis of arterial reconstruction.

Focal Adhesion Kinase Regulates Smooth Muscle Cell Recruitment to the Developing Vasculature

The investment of newly formed endothelial cell tubes with differentiated smooth muscle cells (SMC) is critical for appropriate vessel formation, but the underlying mechanisms remain unknown. We previously showed that depletion of focal adhesion kinase (FAK) in the nkx2.5 expression domain led to aberrant outflow tract (OFT) morphogenesis and strove herein to determine the cell types and mechanisms involved. We crossed fak(loxp) targeted mice with available Cre drivers to deplete FAK in OFT SMC (FAK(wnt) and FAK(nk)) or coronary SMC (FAK(cSMC)). In each case, depletion of FAK led to defective vasculogenesis that was incompatible with postnatal life. Immunohistochemical analysis of the mutant vascular structures revealed that FAK was not required for progenitor cell proliferation, survival, or differentiation into SMC but was necessary for subsequent SMC recruitment to developing vasculature. Using a novel FAK-null SMC culture model, we found that depletion of FAK did not influence SMC growth or survival, but blocked directional SMC motility and invasion toward the potent endothelial-derived chemokine, platelet-derived growth factor PDGFBB. FAK depletion resulted in unstable lamellipodial protrusions due to defective spatial-temporal activation of the small GTPase, Rac-1, and lack of Rac1-dependent recruitment of cortactin (an actin stabilizing protein) to the leading edge. Moreover, FAK null SMC exhibited a significant reduction in stimulated extracellular matrix degradation. FAK drives PDGFBB-stimulated SMC chemotaxis/invasion and is essential for SMC to appropriately populate the aorticopulmonary septum and the coronary vascular plexus.

Immune modulation and increased neurotrophic factor production in multiple sclerosis patients treated with testosterone

BackgroundMultiple sclerosis is a chronic inflammatory disease of the central nervous system with a pronounced neurodegenerative component. It has been suggested that novel treatment options are needed that target both aspects of the disease. Evidence from basic and clinical studies suggests that testosterone has an immunomodulatory as well as a potential neuroprotective effect that could be beneficial in MS.MethodsTen male MS patients were treated with 10 g of gel containing 100 mg of testosterone in a cross-over design (6 month observation period followed by 12 months of treatment). Blood samples were obtained at three-month intervals during the observation and the treatment period. Isolated blood peripheral mononuclear cells (PBMCs) were used to examine lymphocyte subpopulation composition by flow cytometry and ex vivo protein production of cytokines (IL-2, IFNγ, TNFα, IL-17, IL-10, IL-12p40, TGFβ1) and growth factors (brain-derived neurotrophic factor BDNF, platelet-derived growth factor PDGF-BB, nerve growth factor NGF, and ciliary neurotrophic factor CNTF). Delayed type hypersensitivity (DTH) skin recall tests were obtained before and during treatment as an in vivo functional immune measure.ResultsTestosterone treatment significantly reduced DTH recall responses and induced a shift in peripheral lymphocyte composition by decreasing CD4+ T cell percentage and increasing NK cells. In addition, PBMC production of IL-2 was significantly decreased while TGFβ1 production was increased. Furthermore, PBMCs obtained during the treatment period produced significantly more BDNF and PDGF-BB.ConclusionThese results are consistent with an immunomodulatory effect of testosterone treatment in MS. In addition, increased production of BDNF and PDGF-BB suggests a potential neuroprotective effect.Trial RegistrationNCT00405353

Treatment with bone marrow‐derived stromal cells accelerates wound healing in diabetic rats

Bone marrow stem cells participate in tissue repair processes and may have a role in wound healing. Diabetes is characterised by delayed and poor wound healing. We investigated the potential of bone marrow-derived mesenchymal stromal cells (BMSCs) to promote healing of fascial wounds in diabetic rats. After manifestation of streptozotocin (STZ)-induced diabetic state for 5 weeks in male adult Sprague-Dawley rats, healing of fascial wounds was severely compromised. Compromised wound healing in diabetic rats was characterised by excessive polymorphonuclear cell infiltration, lack of granulation tissue formation, deficit of collagen and growth factor [transforming growth factor (TGF-beta), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor PDGF-BB and keratinocyte growth factor (KGF)] expression in the wound tissue and significant decrease in biomechanical strength of wounds. Treatment with BMSC systemically or locally at the wound site improved the wound-breaking strength (WBS) of fascial wounds. The improvement in WBS was associated with an immediate and significant increase in collagen levels (types I-V) in the wound bed. In addition, treatment with BMSCs increased the expression of growth factors critical to proper repair and regeneration of the damaged tissue moderately (TGF-beta, KGF) to markedly (EGF, VEGF, PDGF-BB). These data suggest that cell therapy with BMSCs has the potential to augment healing of the diabetic wounds.