Serum Platelet-derived Growth Factor Levels Research Articles

Features of the regulation of reparative processes of chronic wounds in response to the effect of photobiomodulation therapy on a wound defect. Photobiomodulation therapy for chronic wounds.

One of the promising methods of influencing the wound process is photobiomodulation (PBM) therapy. The optimal parameters of PBM therapy have not yet been found because the molecular mechanisms of light interaction with tissue are not fully understood. Studying the influence of PBM of various parameters on the regulation of reparative process- es of chronic wounds using the example of indicators of aggregation activity of platelets, platelet-derived growth factor (PDGF), interleukin-8 (IL-8), and amino-terminal propeptide of type III procollagen (PIIINP) at the remodeling stage. And also the study of the structural and functional features of chronic wound heal- ing in an experiment under various parameters of PBM therapy. Experiments were carried out on Wistar rats. Chronic wounds were simulated. Experimental animals were exposed to PBM at a wavelength of 660 nm and an energy density of 1 J/cm2. In serum, PDGF, IL-8, and PIIINP levels were measured by enzyme-linked immunosorbent assay. The functional activity of platelets was measured using the turbidimetric method. Histological analysis was performed. The work noted the dose-dependent effect of PBM using the example of platelet aggregation at the remodeling stage during the healing of chronic wounds. The use of PBM therapy resulted in increased serum PDGF levels. Histological examination data indicate a positive effect of PBM therapy on the wound healing process. The effectiveness of the use of PBM therapy for the healing of chronic wounds to regulate reparative processes has been proven.

Interleukin-11 in idiopathic pulmonary fibrosis: predictive value of prognosis and acute exacerbation.

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease with a poor prognosis and unknown aetiology. We have recently clarified the prognostic value of the serum platelet-derived growth factor (PDGF) level in patients with IPF. Interleukin (IL)-11 is a member of the IL-6 family, and in vivo and in vitro studies have suggested that it has profibrotic effects in pulmonary fibrosis. In this study, we investigated the predictive value of the serum IL-11 level in patients with IPF for survival and occurrence of acute exacerbation (AE). This retrospective study included 68 patients with IPF diagnosed according to the 2018 guideline. Serum PDGF levels were measured using the Bio-Plex method and serum IL-11 levels using enzyme-linked immune-sorbent assay. Cytokine production per lung volume was evaluated using the serum cytokine/percent predicted forced vital capacity (%FVC) value. Forty-six patients were male and the median age was 67 years. The serum IL-11/%FVC value was significantly correlated with the percent predicted diffusing capacity of carbon monoxide (ρ=-0.518, P<0.001) and modified Medical Research Council score for shortness of breath (mMRC) (ρ=0.335, P=0.006) by Spearman's rank correlation analysis. Multivariate Cox proportional hazard regression analysis revealed that the serum IL-11/%FVC value was a significant prognostic factor after adjustment for the serum PDGF/%FVC value and other clinical parameters including mMRC and lymphocyte percentage in bronchoalveolar lavage [hazard ratio (HR): 88.540, 95% confidence interval (CI): 1.905-4,115.686, P=0.022]. IL-11/%FVC value was also a significant predictor of AE after adjustment for age and PDGF/%FVC (HR: 1,815.443, 95% CI: 10.49-314,109.219, P=0.004). The serum IL-11/%FVC value was an independent predictor of prognosis and AE occurrence in patients with IPF, and the IL-11 level appeared to show pathophysiologic value in IPF.

Serum Levels of PDGF, EGF, and sFlt-1 in Patients with Polycystic Ovary Syndrome and Their Predictive Effects on Pregnancy Outcomes.

Polycystic ovary syndrome (PCOS) is a neuroendocrine disease with complex etiology characterized by infrequent menstruation, follicular developmental disorders, insulin resistance, and hyperandrogenism. PCOS patients often suffer from anovulatory infertility, and even after successful pregnancy promotion, spontaneous abortion is easy to occur. At present, PCOS is mainly diagnosed by auxiliary examinations such as sex hormones and B ultrasonography, and there is a lack of specific serological markers for the diagnosis of diseases. Similarly, there is a lack of effective evaluation methods for the risk of abortion in PCOS patients. Therefore, it is extremely important to explore the factors that affect the occurrence of abortion in PCOS patients and to find specific indicators that can guide the pregnancy outcome of PCOS patients. The purpose of this study was to investigate the serum levels of platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) in PCOS patients and analyze their predictive effects on the pregnancy outcomes of PCOS patients. The results showed that serum PDGF, EGF, and sFlt-1 levels were secreted abnormally in PCOS patients with abortion and were closely related to the pregnancy outcome of PCOS patients. The combination of the three levels has the highest value in predicting the pregnancy outcome of PCOS patients, which is worth promoting.

The Role of Vitamin D, Platelet-Derived Growth Factor and Insulin-Like Growth Factor 1 in the Progression of Thyroid Diseases

Background:Thyroid cancer (TC) is a common malignant tumor, however the role of total vitamin D: 25(OH)D, Platelet Derived Growth Factor (PDGF) and Insulin Like Growth Factor 1 (IGF-1) in the development of TC is still unclear. Aim:To assess the roles of 25(OH)D, PDGF and IGF-1 in the progression of thyroid diseases. METHODS: The serum levels of 25(OH)D, PDGF and IGF-1 were assessed in 70 patients with papillary thyroid cancer (PTC), 60 patients with benign thyroid nodules (BN) compared to 60 normal controls (NC) using ELISA technique. Results:There was a significant decrease in the serum level of 25(OH)D in TC patients compared to NC (P<0.001) and BN patients (P=0.006). There was a significant increase in the serum levels of PDGF and IGF-1 in TC patients (P<0.001), and BN patients (P<0.001) compared to NC, while there were no significant differences between TC and BN (P=0.087, and 0.258; respectively). PDGF correlated significantly with IGF-1 (r=0.412, P<0.001), TSH (r=0.146, P=0.045), and inversely correlated with 25(OH)D (r= -0.156, P=0.013) and FT4 (r=-0.178, P=0.014). There was a significant inverse correlation between the serum levels of IGF-1 and FT4 (r=-0.172, P=0.017). Sensitivity and specificity for assessment of TC patients were (65.7% and 58.3%, P= 0.001) for 25(OH)D, (65.7% and 58.3%, P=0.021) for IGF-1, and (68.6% and 61.7%, P=0.006) for PDGF. Multivariate analysis demonstrated that serum 25(OH)D (OR=0.578, 95%CI= 0.426-0.783), IGF-1 (OR=1.019, 95%CI= 1.010-1.029) and PDGF (OR=1.007, 95%CI= 1.004-1.009) were considered independent risk factors for thyroid cancer (P<0.001, for all). Conclusion:25(OH) D, IGF-1 and PDGF are significantly different in TC and BN cases compared to control. They have an important role in the progression of TC. However, these data should be validated on a larger sample size.

Platelet-Derived Growth Factor C in Alcoholics

Platelet-derived growth factor (PDGF) promotes liver collagen deposition, acting on hepatic stellate cells. Despite this, low serum PDGF levels were reported in chronic hepatitis C or B infection, although some studies yield the opposite result. Since PDGF may be related not only to fibrosis but also with vascular, neuronal or muscle disease, it is important to analyze its behavior in alcoholics. In total, 17 controls and 62 alcoholic patients consecutively admitted to the hospitalization unit of the Internal Medicine Service were included. We determined serum levels of PDGF C, routine laboratory evaluation, tumor necrosis factor-α, interleukin (IL)-6 and IL-8 and malondialdehyde (MDA) levels. We analyzed the relationships between PDGF and liver function, ethanol intake and inflammatory reaction by both univariate and multivariate analysis to discern which variables PDGF levels depend on. Serum PDGF levels were significantly lower among patients (675±466pg/ml) than among controls (1074±337pg/ml; Z=3.70; P<0.001), and even lower among cirrhotics (549±412 among cirrhotics vs 778±487 among non-cirrhotics; Z=2.33; P=0.02). PDGF levels showed a direct correlation with prothrombin activity (ρ=0.50; P<0.001), platelet count (ρ=0.44; P<0.001) and inverse ones with bilirubin (ρ=-0.39; P=0.002), IL-6 (ρ=-0.33; P=0.016), IL-8 (ρ=-0.47; P<0.001), and MDA levels (ρ=-0.44; P<0.001). By multivariate analysis, only prothrombin activity and platelet count were independently related to PDGF. PDGF-C levels are decreased in alcoholics, especially among cirrhotics. Multivariate analysis discloses that only prothrombin activity and platelet count are independently related to PDGF-C levels.

Enhanced PDGF signaling in gestational diabetes mellitus is involved in pancreatic β-cell dysfunction

Gestational diabetes mellitus (GDM) is often accompanied by the development of hyperinsulinemia as an adaptation to increased insulin demand, but this subsequently causes insulin resistance. Loss of function in pancreatic β-cells further aggravates the development of GDM. The level of serum platelet-derived growth factor (PDGF) reportedly increases in GDM patients. The present study investigated whether enhanced PDGF signaling directly causes β-cell dysfunction during gestation. Serum PDGF levels were negatively correlated with β-cell function in GDM patients. Administration of PDGF-BB disrupted glucose tolerance and β-cell function without inducing apoptosis in gestational mice but had no similar effect in non-gestational mice. The β-cell-specific genes encoding insulin synthesis proteins were decreased in the islets of PDGF-BB-treated gestational mice. In vitro experiments using INS1 insulinoma cells showed that PDGF-BB promoted cell proliferation, whereas it downregulated β-cell-specific genes. Taken together, these findings suggested that PDGF reduces β-cell function during gestation possibly through β-cell dedifferentiation.

Cardiac rehabilitation programme as a non-pharmacological platelet inhibitory tool in acute coronary syndrome survivors.

Background Acute coronary syndrome is associated with platelet hyperactivity, which in its persistent form, promotes recurrent thrombotic events. Complex cardiac rehabilitation after acute coronary syndrome improves clinical outcome; however, its effect on platelet hyperactivity is unknown. Design and methods We enrolled 84 acute coronary syndrome patients on dual antiplatelet therapy, who underwent a new complex cardiac rehabilitation programme (NovaCord physiotherapy, lifestyle counselling, strict diet, stress management and regular coaching) and 51 control acute coronary syndrome patients with traditional cardiac rehabilitation. Platelet functionality was determined at enrolment and at three months follow-up by aggregometry, serum platelet-derived growth factor levels, total- and platelet-derived microvesicle counts (PMV; CD41a+/CD61+, CD62P+). Results Platelet aggregation parameters and platelet-derived growth factor levels were significantly decreased in the complex cardiac rehabilitation group at three months (1 µg/ml collagen, median (interquartile range): 22 (10-45) vs 14 (7.5-25.5)%, p = 0.0015; 2 µg/ml collagen: 36 (22-60) vs 26.5 (16-37)%, p = 0.0019; 1.25 µM adenosine-diphosphate: 4.5 (1-10) vs 1 (0-3)%, p = 0.0006; 5 µM adenosine-diphosphate: 27 (16-38) vs 22 (12-31)%, p = 0.0078; epinephrine: 33 (15-57) vs 27 (12-43)%, p = 0.01; platelet-derived growth factor: 434.6 (256.0-622.7) vs 224.8 (148.5-374.1) pg/ml, p = 0.0001). In contrast, these changes were absent or did not reach statistical significance in the traditional cardiac rehabilitation group. Platelet-derived microvesicle counts were significantly decreased in both groups, while total microvesicle count was significantly reduced only in the complex cardiac rehabilitation group (median (interquartile range): 3945.5 (2138-5661) vs 1739 (780-2303) count/µl; p = 0.0001). Conclusions Platelet hyperactivity three months after acute coronary syndrome significantly decreased in patients undergoing complex cardiac rehabilitation. Besides dual antiplatelet therapy, effective management and comprehensive control of cardiovascular risk factors might represent a new, non-pharmacological approach to influence platelet functionality.

Role of xenogenous bovine platelet gel embedded within collagen implant on tendon healing: an invitro and invivo study.

Surgical reconstruction of large Achilles tendon defects is demanding. Platelet concentrates may be useful to favor healing in such conditions. The characteristics of bovine platelet-gel embedded within a collagen-implant were determined invitro, and its healing efficacy was examined in a large Achilles tendon defect in rabbits. Two cm of the left Achilles tendon of 60 rabbits were excised, and the animals were randomly assigned to control (no implant), collagen-implant, or bovine-platelet-gel-collagen-implant groups. The tendon edges were maintained aligned using a Kessler suture. No implant was inserted in the control group. In the two other groups, a collagen-implant or bovine-platelet-gel-collagen-implant was inserted in the defect. The bioelectricity and serum platelet-derived growth factor levels were measured weekly and at 60 days post injury, respectively. After euthanasia at 60 days post injury, the tendons were tested at macroscopic, microscopic, and ultrastructural levels, and their dry matter and biomechanical performances were also assessed. Another 60 rabbits were assigned to receive no implant, a collagen-implant, or a bovine-platelet-gel-collagen-implant, euthanized at 10, 20, 30, and 40 days post injury, and their tendons were evaluated grossly and histologically to determine host-graft interactions. Compared to the control and collagen-implant, treatment with bovine-platelet-gel-collagen-implant improved tissue bioelectricity and serum platelet-derived growth factor levels, and increased cell proliferation, differentiation, and maturation. It also increased number, diameter, and density of the collagen fibrils, alignment and maturation of the collagen fibrils and fibers, biomechanical properties and dry matter content of the injured tendons at 60 days post injury. The bovine-platelet-gel-collagen-implant also increased biodegradability, biocompatibility, and tissue incorporation behavior of the implant compared to the collagen-implant alone. This treatment also decreased tendon adhesion, muscle fibrosis, and atrophy, and improved the physical activity of the animals. The bovine-platelet-gel-collagen-implant was effective in neotenon formation invivo, which may be valuable in the clinical setting.

Acupuncture Combined with Curcumin Disrupts Platelet-Derived Growth Factor β Receptor/Extracellular Signal-Regulated Kinase Signalling and Stimulates Extracellular Matrix Degradation in Carbon Tetrachloride-Induced Hepatic Fibrosis in Rats

Acupuncture treatment has been increasingly used to treat chronic liver diseases. We previously reported that acupuncture combined with curcumin, a natural antifibrotic compound, could remarkably attenuate liver fibrosis in chemically intoxicated rats, but the underlying molecular mechanisms are poorly understood. The present study was aimed at investigating the effects of acupuncture combined with curcumin on platelet-derived growth factor (PDGF) signalling and extracellular matrix (ECM) regulation in the fibrotic liver. A total of 60 Sprague-Dawley male rats were randomly divided into control, model, sham, acupuncture, curcumin and combination treatment groups. During the establishment of fibrosis using carbon tetrachloride (CCl(4)), acupuncture at LR3, LR14, BL18 and ST36 and/or curcumin treatment by mouth were performed simultaneously. After treatment, serum PDGF levels were measured. Protein and mRNA expression of key effectors in PDGF pathway and fibrinolysis in the liver was determined. Acupuncture combined with curcumin potently reduced serum PDGF levels and selectively disrupted the PDGF-βR/extracellular signal-regulated kinase (ERK) cascade. Combination treatment also significantly repressed expression of connective tissue growth factor and upregulated expression of matrix metalloproteinase-9, promoting fibrinolysis in the fibrotic liver. The beneficial effects of acupuncture and its combination with curcumin could be attributed to the disruption of PDGF-βR/ERK pathway and stimulated ECM degradation in the fibrotic liver. Acupuncture treatment significantly enhanced curcumin effects at the molecular level. These findings may provide molecular insights into the potential of acupuncture combined with curcumin for prevention of hepatic fibrosis.

Serum growth factors in asbestosis patients

Various growth factors, including platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-β, have been implicated in the pathogenesis of asbestos-induced disease. PDGF and TGF-β levels were determined by enzyme-linked immunosorbent assays in the banked serum samples of a cohort of workers with asbestosis, and the relationships of the growth factor levels to the subsequent development of cancer and to the radiographic severity and progression of asbestosis in the cohort were examined. Serum levels of PDGF and TGF-β were found to be unrelated to the development of cancer, and serum levels of PDGF were found to be unrelated to the severity and progression of asbestosis. However, serum levels of TGF-β were found to be statistically significantly related to disease severity (p = 0.01), increasing approximately 2.4-fold from ILO radiographic category 0 to category 3, and they were marginally related to disease progression (p = 0.07), in multivariate analysis controlling for other contributory factors including cumulative asbestos exposure. This suggests that serum TGF-β may be a useful biomarker for asbestos-induced fibrotic disease.

Cytokine profiles in serum and peritoneal fluid from infertile women with and without endometriosis

To study the serum and peritoneal fluid cytokine profiles in infertile women with minimal/mild active endometriosis. Fifty-seven consecutive infertile women undergoing laparoscopy for unexplained infertility had peritoneal fluid and serum samples obtained at the time of laparoscopy. The levels of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 beta (IL-1 beta), vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotatic protein-1 (MCP-1), RANTES, platelet derived growth factor (PDGF), soluble Fas (sFas), and soluble Fas Ligand (sFasL) in peritoneal fluid and serum were measured to compare the concentration in both biological fluids, in women who have minimal/mild red endometriosis using women with no endometriosis as controls. Peritoneal fluid levels of MCP-1, IL-8 and IL-6 were significantly higher in the endometriosis group (P < 0.012, P = 0.003, and P = 0.015, respectively). There was no significant difference in the peritoneal fluid levels of IL-1 beta, TNF-alpha, RANTES, VEGF, PDGF, sFas and sFasL in the two groups. Although serum levels of IL-8 were higher in women with endometriosis, the difference was not significant (P = 0.07). Serum levels of PDGF, IL-6, RANTES, IL-1 beta, TNF-alpha, and sFas, were not significantly different in the two groups. The elevated levels of MCP-1, IL-6, and IL-8 in peritoneal fluid but not serum may indicate the importance of local macrophage activating factors in the pathogenesis of endometriosis.

Role of platelet-derived growth factor and transforming growth factor β 1 the in the regulation of metalloproteinase expressions

We investigated the role and influence of platelet derived growth factor (PDGF) and transforming growth factor beta1 (TGF) in the pathologic mechanism at the basis of plaque instability regulating the expression of matrix metalloproteinases (MMPs). Plaques obtained from 70 patients who underwent carotid endarterectomy were classified histologically as stable or unstable. Serum levels of PDGF and TGF were measured pre- and postoperatively. The serum activities of MMP-2 and MMP-9 were also analyzed. Human umbilical artery smooth muscle cells (HUASMCs) were stimulated in vitro with PDGF at various concentrations (20 and 50 ng/mL) and TGF (2 and 5 ng/mL) in a serum-free medium. The release of MMPs in the conditioned medium was assessed by enzyme-linked immunosorbent assay. Release of the MMPs was confirmed by Western blot analysis; their activity and expression were determined by zymography and reverse transcription-polymerase chain reaction. Specific inhibition tests were performed on HUASMCs to evaluate the role of these growth factors. Forty-two (60%) patients had an unstable carotid plaque and 28 (40%) a stable plaque. Preoperatively, patients affected with unstable carotid plaques had higher PDGF and lower TGF plasma levels than patients with stable carotid plaques (P < .001); the levels returned to normal at 1 and 30 days postoperatively, compared with 20 non-operated healthy volunteers. Release, activity, protein level, and expression of MMPs in PDGF-stimulated HUASMCs were greater than in the controls (P < .001), whereas these values in the TGF-stimulated HUASMCs were lower (P < .001). The addition of monoclonal anti-PDGF antibodies decreased the release, activity, protein level, and expression of MMPs, whereas the addition of monoclonal anti-TGF antibodies increased the release, activity, protein level and expression of MMPs (P < .001). TGF seems to be an important stabilizing factor and prevents plaque rupture through the decrease of MMPs.

Abundant expression of platelet-derived growth factor in spiral arteries in decidua associated with pregnancy-induced hypertension and its relevance to atherosis.

To elucidate the role of platelet-derived growth factor (PDGF) in the pathophysiology of pregnancy-induced hypertension (PIH) in which the spiral arteries of the decidua demonstrate the atherosclerotic change. We determined serum levels of PDGF and PDGF expression in the decidua as well as serum levels of 17 beta-estradiol (E2) and progesterone (P4) both in normotensive cases and in PIH cases. Furthermore, we investigated whether sex steroid hormones could interact with PDGF in cultured vascular smooth muscle cells (SMC) by immunohistochemical staining for proliferating cell nuclear antigen. Serum PDGF levels were higher (P<0.01) but serum E2 levels were lower (P<0.01) in PIH cases compared with normotensive cases. There was no statistically significant difference between serum P4 levels in PIH cases and those in normotensive cases. Immunohistochemical staining for PDGF in SMC of spiral arteries was more prominent in PIH cases than in normotensive cases. The proliferative potential of cultured SMC was stimulated by PDGF, but inhibited by concomitant treatment with PDGF and E2. PDGF is suggested to play an important role in the pathophysiology of PIH through its stimulatory effect on vascular SMC proliferation which may elicit the atherosclerotic change in the spiral arteries of the placenta.

Immunoassay of platelet-derived growth factor in the blood of patients with diabetes mellitus

Platelet-derived growth factor (PDGF) is a powerful mitogen for many cell types, and is believed to play a major role in wound healing when released from platelets at sites of injury. In diabetes mellitus, it has been proposed that premature release of PDGF from platelets impairs the ability of platelets to initiate healing, and also accelerates the development of diabetic complications such as angiopathy by increasing plasma-borne PDGF. However, plasma samples from diabetic patients have not previously been assayed for PDGF using suitable techniques. A sensitive monoclonal enzyme-linked immunoassay for PDGF was applied to plasma and serum samples from 18 healthy control subjects and 60 diabetic patients. Neither plasma nor serum PDGF concentrations differed significantly between control subjects, insulin-dependent, and non-insulin-dependent diabetic patients. However, 23% of the diabetic subjects had serum PDGF levels above the control range. Limited joint mobility, which is characterised by joint contractures and collagen deposition in the skin, and is associated with microvascular disease, was used as a marker of diabetic complications. Limited joint mobility affected 43% of the diabetic subjects. Patients with moderate limited joint mobility had had diabetes significantly longer than those without limited joint mobility (means 17 years and 9 years, respectively, p = 0.008). However, limited joint mobility was not associated with elevated serum or plasma PDGF in insulin-dependent or non-insulin-dependent diabetes. We conclude that complications of diabetes are unlikely to be caused by changes in systemic levels of PDGF.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunoassay of platelet-derived growth factor in the blood of patients with diabetes mellitus

Platelet-derived growth factor (PDGF) is a powerful mitogen for many cell types, and is believed to play a major role in wound healing when released from platelets at sites of injury. In diabetes mellitus, it has been proposed that premature release of PDGF from platelets impairs the ability of platelets to initiate healing, and also accelerates the development of diabetic complications such as angiopathy by increasing plasma-borne PDGF. However, plasma samples from diabetic patients have not previously been assayed for PDGF using suitable techniques. A sensitive monoclonal enzyme-linked immunoassay for PDGF was applied to plasma and serum samples from 18 healthy control subjects and 60 diabetic patients. Neither plasma nor serum PDGF concentrations differed significantly between control subjects, insulin-dependent, and non-insulin-dependent diabetic patients. However, 23% of the diabetic subjects had serum PDGF levels above the control range. Limited joint mobility, which is characterised by joint contractures and collagen deposition in the skin, and is associated with microvascular disease, was used as a marker of diabetic complications. Limited joint mobility affected 43% of the diabetic subjects. Patients with moderate limited joint mobility had had diabetes significantly longer than those without limited joint mobility (means 17 years and 9 years, respectively, p=0.008). However, limited joint mobility was not associated with elevated serum or plasma PDGF in insulin-dependent or non-insulin-dependent diabetes. We conclude that complications of diabetes are unlikely to be caused by changes in systemic levels of PDGF. The delayed healing associated with diabetes is not due to a deficit in PDGF available from platelets.