Plasma Vascular Endothelial Growth Factor Research Articles

Levels of melatonin and some indicators of angiogenesis, antioxidant system and lipid peroxidation in blood plasma in women with uterine leiomyoma

Uterine leiomyoma is one of the most common gynaecological diseases, which often leads to loss of fertility. It is known that in this pathology, damage to the tissues of the uterus is accompanied by oxidative stress, and the mechanisms of its compensation play a decisive role in the process of myometrial regeneration, especially when performing organ-preserving operations. The aim of the study was to determine the levels of melatonin, reproductive hormones and state of angiogenesis, antioxidant system and lipid peroxidation in women of reproductive age who were diagnosed with uterine leiomyoma. Material and methods. 60 women of reproductive age with uterine leiomyoma (study group) were examined. The control group consisted of 20 healthy women of the same age group. Melatonin levels in women's blood were determined once, on an empty stomach, at 8 a.m.; the concentrations of estradiol and progesterone in the follicular phase of the menstrual cycle were also measured. The state of the angiogenesis system was studied by examining the levels of vascular endothelial growth factor (VEGF) and the content of the final metabolites of nitric oxide NO in blood plasma. The activity of the antioxidant system was assessed by blood plasma concentrations of reduced glutathione, glutathione peroxidase, and glutathione transferase. Indicators of lipid peroxidation were investigated by the content of malondialdehyde (MDA) in blood plasma and erythrocytes. Results. It was found that in the patients of the study group with leiomyoma, there was a significantly lower level of melatonin in blood plasma (111.1 ± 18.5 ng/mL) compared to the control group (153.5 ± 8.5 ng/mL), while the concentration of estradiol was almost three times higher (107.4 ± 25.3 pg/mL) compared to the control group (36.2 ± 3.2 pg/mL), and the concentration of progesterone was 1.9 times higher (2.1 ± 0.4 ng/mL compared to 1.1 ± 0.5 ng/mL in the control group). The level of VEGF in blood plasma in women with uterine leiomyoma was also higher (90.4 ± 23.6 pg/mL) compared to the control group (35.1 ± 8.3 pg/mL), as well as the concentration of final metabolites of nitric oxide, which reached 25.3 ± 5.9 pg/mL compared to 9.9 ± 3.9 pg/mL in the control group. The reduced glutathione level in the blood plasma of women with uterine leiomyoma was significantly lower (0.77 ± 0.13 µmol/L) compared to healthy women (1.02 ± 0.14 µmol/L) in the control group, while the concentrations of glutathione-S-transferase and glutathione peroxidase enzymes were higher (161.3 ± 22.3 ng/mL and 235.7 ± 35.9 ng/mL, respectively), whereas in the control group these indicators were 118.9 ± 18.0 ng/mL and 105.3 ± 41.2 ng/mL, respectively. The MDA content in women of the study group was higher, measuring 5.2 ± 0.8 nmol/L in plasma and 10.8 ± 1.1 nmol/L in erythrocytes compared to 2.3 ± 0.8 nmol/L and 5.3 ± 0.8 nmol/L in the control group, respectively. Conclusions. The levels of melatonin and reduced glutathione in the blood plasma of women with uterine leiomyoma were significantly lower, while the concentrations of estradiol, progesterone, glutathione-S-transferase, glutathione peroxidase, VEGF, final metabolites of nitric oxide, as well as the average MDA content in plasma and erythrocytes, were significantly higher compared to healthy women. In the study group, the relationship between the level of progesterone in blood plasma and the content of malondialdehyde in erythrocytes was described using a linear regression equation, which, as we suggest, indicates an activating effect of progesterone on oxidative stress mechanisms in the myometrium. In our opinion, oxidative stress in uterine leiomyoma occurs due to inadequate activity of the antioxidant system, an integral part of which is melatonin, leading to enhanced angiogenesis against the background of estrogen-induced myometrial proliferation.

Intravitreal aflibercept confounds interpretation of plasma VEGF (vascular endothelial growth factor) levels in POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome.

Intravitreal aflibercept confounds interpretation of plasma VEGF (vascular endothelial growth factor) levels in POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome.

Plasma sPD-L1 and VEGF levels are associated with the prognosis of NSCLC patients treated with combination immunotherapy.

The clinical significance of plasma soluble programmed cell death ligand 1 (sPD-L1) and vascular endothelial growth factor (VEGF) for non-small cell lung cancer (NSCLC) treated with the combination of anti-angiogenic therapy and anti-PD-L1 antibody (Ab) remain unknown. This study aimed to explore the association between plasma sPD-L1 and VEGF levels and the prognosis of NSCLC patients treated with the combination of Envafolimab and Endostar. Peripheral blood samples were collected from 24 NSCLC patients at baseline and after 6 weeks of treatment and were detected for sPD-L1 and VEGF levels. Both baseline and posttreatment sPD-L1 were significantly higher in progressive disease (PD) group than in controlled disease (CD) group (median: 77.5 pg/ml vs. 64.6 pg/ml, P = 0.036, median: 8451 pg/ml vs. 5563 pg/ml, P = 0.012). In multivariate analysis, lower baseline sPD-L1 levels were significantly associated with longer progression-free survival (PFS) (HR = 6.834, 95% CI: 1.350-34.592, P = 0.020). There were significantly higher posttreatment VEGF levels in PD group compared with CD group (median: 323.7 pg/ml vs. 178.5 pg/ml, P = 0.009). Higher posttreatment VEGF levels were significantly associated with shorter PFS in multivariate analysis (HR = 5.911, 95% CI: 1.391-25.122, P = 0.016). Plasma sPD-L1 and VEGF levels are associated with the clinical response and prognosis of NSCLC patients treated with the combination of PD-L1 inhibitors and anti-angiogenetic therapy.

Plasma VEGFA and PGF impact longitudinal tau and cognition in preclinical Alzheimer's disease.

Vascular dysfunction is increasingly recognized as an important contributor to the pathogenesis of Alzheimer's disease. Alterations in vascular endothelial growth factor (VEGF) pathways have been implicated as potential mechanisms. However, the specific impact of VEGF proteins in preclinical Alzheimer's disease and their relationships with other Alzheimer's disease and vascular pathologies during this critical early period remain to be elucidated. We included 317 older adults from the Harvard Aging Brain Study, a cohort of individuals who were cognitively unimpaired at baseline and followed longitudinally for up to 12 years. Baseline VEGF family protein levels (VEGFA, VEGFC, VEGFD, PGF, and FLT1) were measured in fasting plasma using high-sensitivity immunoassays. Using linear mixed effects models, we examined the interactive effects of baseline plasma VEGF proteins and amyloid PET burden (Pittsburgh Compound-B) on longitudinal cognition (Preclinical Alzheimer Cognitive Composite-5). We further investigated if effects on cognition were mediated by early neocortical tau accumulation (Flortaucipir PET burden in the inferior temporal cortex) or hippocampal atrophy. Lastly, we examined the impact of adjusting for baseline cardiovascular risk score or white matter hyperintensity volume. Baseline plasma VEGFA and PGF each showed a significant interaction with amyloid burden on prospective cognitive decline. Specifically, low VEGFA and high PGF were associated with greater cognitive decline in individuals with elevated amyloid, i.e. those on the Alzheimer's disease continuum. Concordantly, low VEGFA and high PGF were associated with accelerated longitudinal tau accumulation in those with elevated amyloid. Moderated mediation analyses confirmed that accelerated tau accumulation fully mediated the effects of low VEGFA and partially mediated (31%) the effects of high PGF on faster amyloid-related cognitive decline. The effects of VEGFA and PGF on tau and cognition remained significant after adjusting for cardiovascular risk score or white matter hyperintensity volume. There were concordant but non-significant associations with longitudinal hippocampal atrophy. Together, our findings implicate low VEGFA and high PGF in accelerating early neocortical tau pathology and cognitive decline in preclinical Alzheimer's disease. Additionally, our results underscore the potential of these minimally-invasive plasma biomarkers to inform the risk of Alzheimer's disease progression in the preclinical population. Importantly, VEGFA and PGF appear to capture distinct effects from vascular risks and cerebrovascular injury. This highlights their potential as new therapeutic targets, in combination with anti-amyloid and traditional vascular risk reduction therapies, to slow the trajectory of preclinical Alzheimer's disease and delay or prevent the onset of cognitive decline.

The Relationship between COVID-19 Severity and Plasma Levels of Vascular Endothelial Growth Factor (VEGF)

Background: This study aimed to assess the relationship between COVID-19 severity and the plasma levels of vascular endothelial growth factor. Methods: This cross-sectional study was conducted on 86 patients with COVID-19. A 5 ml venous blood sample was taken on the first day of hospitalization. VEGF was measured with the ELISA method using the Hangzhou East biopharm VEGF ELIZA Kit. Results: Although plasma VEGF levels were higher in the severe group than in the non-severe group, no significant relationship was found between the plasma level of VEGF and COVID-19 severity, which might be due to the small sample size. VEGF may be a valuable scientific marker, but in this study, it was not as useful as other markers in identifying COVID-19 severity. In addition, there was a direct and significant relationship between COVID-19 severity and the inflammatory markers LDH, neutrophil/lymph, and CRP. Therefore, measurement of inflammatory markers can assist in the early identification and prediction of severity and disease progression in COVID-19. Conclusion: Although plasma VEGF levels were higher in the severe group than in the non-severe group, no significant relationship was found between the plasma level of VEGF and COVID-19 severity, which might be due to the small sample size. VEGF may be a valuable scientific marker, but in this study, it was not as useful as other markers in identifying COVID-19 severity. In addition, there was a direct and significant relationship between COVID-19 severity and the inflammatory markers LDH, neutrophil/lymph, and CRP. Therefore, measurement of inflammatory markers can assist in the early identification and prediction of severity and disease progression in COVID-19.

Efficacy and Safety of Biosimilar QL1207 vs. the Reference Aflibercept for Patients with Neovascular Age-Related Macular Degeneration: A Randomized Phase 3 Trial.

This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD). This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73-34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2mg (0.05ml) in the study eye every 4weeks for the first 3months, followed by 2mg every 8weeks until week 48, stratified by baseline BCVA ≥ or < 45 letters. The primary endpoint was BCVA change from baseline at week 12. The equivalence margin was ± 5 letters. The safety, immunogenicity, pharmacokinetics (PK), and plasma vascular endothelial growth factor (VEGF) concentration were also evaluated. A total of 366 patients were enrolled (QL1207 group, n = 185; aflibercept group, n = 181) from Aug 2019 to Jan 2022 with comparable baseline characteristics. The least-squares mean difference in BCVA changeswas - 1.1 letters(95% confidence interval - 3.0 to 0.7; P = 0.2275) between the two groups, within the equivalence margin. The incidences of treatment-emergent adverse events (TEAE; QL1207: 71.4% [132/185] vs. aflibercept: 71.8% [130/181]) and serious TEAE (QL1207: 14.1% [26] vs. aflibercept: 12.7% [23]) appeared comparable between treatment groups, and no new safety signal was found. Anti-drug antibody, PK profiles, and VEGF concentration were similar between the two groups. QL1207 has equivalent efficacy to aflibercept for nAMD with similar safety profiles. It could be used as an alternative anti-VEGF agent for clinical practice. ClinicalTrials.gov: NCT05345236 (retrospectively registered on April 25, 2022); National Medical Products Administration of China: CTR20190937 (May 20, 2019).

96 Short-Term Blood Pressure Variability and Cerebrovascular Health in OlderaAdults

Objective:Blood pressure variability (BPV), independent of traditionally targeted average blood pressure levels, is an emerging vascular risk factor for stroke, cerebrovascular disease, and dementia, possibly through links with vascular-endothelial injury. Recent evidence suggests visit-to-visit (e.g., over months, years) BPV is associated with cerebrovascular disease severity, but less is known about relationships with short-term (e.g., &lt; 24 hours) fluctuations in blood pressure. Additionally, it is unclear how BPV may be related to angiogenic growth factors that play a role in cerebral arterial health.Participants and Methods:We investigated relationships between short-term BPV, white matter hyperintensities on MRI, and levels of plasma vascular endothelial growth factor (VEGF) in a sample of community-dwelling older adults (n = 57, ages 55-88) without history of dementia or stroke. Blood pressure was collected continuously during a 5-minute resting period. BPV was calculated as variability independent of mean, a commonly used index of BPV uncorrelated with average blood pressure levels. Participants underwent T2-FLAIR MRI to determine severity of white matter lesion burden. Severity of lesions was classified as Fazekas scores (0-3). Participants also underwent venipuncture to determine levels of plasma VEGF. Ordinal logistic regression examined the association between BPV and Fazekas scores. Multiple linear regression explored relationships between BPV and VEGF. Models controlled for age, sex, and average blood pressure.Results:Elevated BPV was related to greater white matter lesion burden (i.e., Fazekas score) (systolic: OR = 1.17 [95% CI 1.01, 1.37]; p = .04; diastolic: OR = 2.47 [95% CI 1.09, 5.90]; p = .03) and increased levels of plasma VEGF (systolic: ß = .39 [95% CI .11, .67]; adjusted R2 = .16; p = .007; diastolic: ß = .48 [95% CI .18, .78]; adjusted R2 = .18; p = .003).Conclusions:Findings suggest short-term BPV may be related to cerebrovascular disease burden and angiogenic growth factors relevant to cerebral arterial health, independent of average blood pressure. Understanding the role of BPV in cerebrovascular disease and vascular-endothelial health may help elucidate the increased risk for stroke and dementia associated with elevated BPV.

Effect of risperidone on plasma vascular endothelial growth factor levels in patients with first-episode schizophrenia: A preliminary study

This study investigated the role of vascular endothelial growth factor (VEGF) in 18 patients with first-episode schizophrenia (FES) and 19 healthy controls and the effect of risperidone monotherapy on plasma VEGF levels. The plasma VEGF levels were measured at baseline and after four weeks of risperidone treatment. We found no difference in baseline VEGF levels between the groups and no change in VEGF levels after risperidone treatment. No correlation was found between VEGF levels and symptom severity. Our findings suggest that VEGF may not serve as a distinguishing biomarker in FES or be directly influenced by risperidone.

Biological and Clinical Implications of the Vascular Endothelial Growth Factor Coreceptor Neuropilin-1 in Human Immunodeficiency Virus.

Plasma vascular endothelial growth factor (VEGF) coreceptor neuropilin-1 (NRP-1) had the largest association with coronary plaque in the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) proteomics analysis. With little known about NRP-1 in people with human immunodeficiency virus (PWH), we explored its relation to other proteins in REPRIEVE and validated our findings through a Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) case-cohort study by assessing its relation to host factors and incident cardiovascular disease and cancer. Within REPRIEVE, NRP-1 was associated with proteins involved in angiogenesis, signal transduction, immunoregulation, and cell migration/adhesion. Within CNICS, NRP-1 was associated with key host factors, including older age and male sex. NRP-1 was associated with an increased hazard of multiple cancers but a decreased prostate cancer risk. Finally, NRP-1 was most strongly associated with mortality and type 2 myocardial infarction. These data suggest that NRP-1 is part of a clinically relevant immunoregulatory pathway related to multiple comorbidities in PWH. Clinical Trials Registration. NCT02344290.

Safety and biodistribution of XC001 (encoberminogene rezmadenovec) gene therapy in rats: a potential therapy for cardiovascular diseases.

Adenovirus-mediated gene therapy holds promise for the treatment of cardiovascular diseases such as refractory angina. However, potential concerns around immunogenicity and vector dissemination from the target injected tissue require evaluation. This study was undertaken to evaluate the safety and biodistribution of XC001, a replication-deficient adenovirus serotype 5 vector expressing multiple isoforms of human vascular endothelial growth factor (VEGF), following direct administration into normal rat myocardium. Animals received the buffer formulation or increasing doses of XC001 (1 × 107, 2.5 × 108 or 2.5 × 109 viral particles). Based on in-life parameters (general health, body weights, clinical pathology, serum cardiac troponin I, plasma VEGF, and gross necropsy), there were no findings of clinical concern. On Day 8, intramyocardial administration of XC001 was associated with dose-related, left ventricular myocardial inflammation at injection sites, resolving by Day 30. XC001 DNA was not detected in blood at any time but was present at Day 8 around the site of injection and to a much lesser extent in the spleen, liver, and lungs, persisting at low levels in the heart and spleen until at least Day 91. These findings demonstrate that intramyocardial injection of XC001 is supported for use in human studies.

Remote ischemic conditioning in the treatment of acute cerebral infarction: A case control study

ObjectiveThis paired case-control study aimed to evaluate the efficacy and safety of remote ischemic conditioning (RIC) in patients with acute cerebral infarction (CI) and explore potential serological markers of RIC. MethodsPatients with acute CI (<72 h) were matched 1:1 according to age, sex, and CI conditions and were divided into the RIC group and the control group. The RIC group received RIC intervention for 7 days on top of routine treatment, while the control group received a sham RIC. The curative effects and adverse reactions were observed. ResultA total of 66 patients (mean age 60.00 ± 11.37 years; mean time of acute CI onset 32.91 ± 17.94 h) completed the study. The National Institute of Health stroke scale score on day 7, modified Rankin Scale scores on day 7 and day 90 were significantly lower than the baseline in the RIC group (P < 0.001, P = 0.003, P = 0.004, respectively) but not in the control group (P = 0.056, P = 0.169, P = 0.058, respectively). RIC was well-tolerated, and no adverse events were reported. Both plasma hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor increased in the RIC group from day 0 to day 7, while they decreased in the control group. The changes in plasma HIF-1α in the RIC group were statistically different from those in the control group (P = 0.006). ConclusionEarly and short-term RIC treatment was well-tolerated and effective in improving the prognosis in acute CI. HIF-1α can be recognized as a biomarker for evaluating the efficacy of RIC treatment.

One Single Tube Reaction of Aptasensor-Based Magnetic Sensing System for Selective Fluorescent Detection of VEGF in Plasma.

In this study, a simple, easy and convenient fluorescent sensing system for the detection of the vascular endothelial growth factor (VEGF) based on VEGF aptamers, aptamer-complementary fluorescence-labeled probe and streptavidin magnetic beads was developed in one single tube. The VEGF is the most important biomarker in cancer, and it is investigated that the serum VEGF level varied according to the different types and courses of cancers. Hence, efficient quantification of VEGF is able to improve the accuracy of cancer diagnoses and the precision of disease surveillance. In this research, the VEGF aptamer was designed to be able to bind with the VEGF by forming G-quadruplex secondary structures; then, the magnetic beads would capture the non-binding aptamers due to non-steric interference; and finally, the fluorescence-labeled probes were hybridized with the aptamers captured by the magnetic beads. Therefore, the fluorescent intensity in the supernatant would specifically reflect the present VEGF. After an overall optimization, the optimal conditions for the detection of VEGF were as followed, KCl, 50 μM; pH 7.0; aptamer, 0.1 μM; and magnetic beads, 10 μL (4 μg/μL). The VEGF could be well quantified within a range of 0.2-2.0 ng/mL in plasma, and the calibration curve possessed a good linearity (y = 1.0391x + 0.5471, r = 0.998). The detection limit (LOD) was calculated to be 0.0445 ng/mL according to the formula (LOD = 3.3 × σ/S). The specificity of this method was also investigated under the appearance of many other serum proteins, and the data showed good specificity in this aptasensor-based magnetic sensing system. This strategy provided a simple, sensitive and selective biosensing platform for the detection of serum VEGF. Finally, it was expected that this detection technique can be used to promote more clinical applications.

VEGF-A related SNPs: a cardiovascular context.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Currently, cardiovascular disease risk algorithms play a role in primary prevention. However, this is complicated by a lack of powerfully predictive biomarkers that could be observed in individuals before the onset of overt symptoms. A key potential biomarker for heart disease is the vascular endothelial growth factor (VEGF-A), a molecule that plays a pivotal role in blood vessel formation. This molecule has a complex biological role in the cardiovascular system due to the processes it influences, and its production is impacted by various CVD risk factors. Research in different populations has shown single nucleotide polymorphisms (SNPs) may affect circulating VEGF-A plasma levels, with some variants associated with the development of CVDs, as well as CVD risk factors. This minireview aims to give an overview of the VEGF family, and of the SNPs reported to influence VEGF-A levels, cardiovascular disease, and other risk factors used in CVD risk assessments.

POEMS syndrome associated with vitiligo (P13-8.007)

<h3>Objective:</h3> To report a case of POEMS syndrome with vitiligo. This is the second case to be reported and the first in an Afro-American patient. <h3>Background:</h3> POEMS syndrome is a rare plasma-cell disorder with multisystem involvement, characterized by the acronym composing its name: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein (M-protein), and Skin changes. Major criteria include mandatory polyneuropathy and monoclonal plasma cell proliferative disorder in addition to Castleman’s disease, sclerotic bone lesions, or elevated vascular endothelial growth factor (VEGF). Minor criteria, still helpful for diagnosis, include organomegaly, endocrinopathy, papilledema, thrombosis, and skin changes, the most common being hyperpigmentation. <h3>Design/Methods:</h3> Case Presentation <h3>Results:</h3> A 50-year-old Afro-American male presented with 3 years of ascending stocking-glove pattern numbness and skin discoloration in his feet. Other positive history included anhidrosis, heat intolerance and erectile dysfunction suggestive of dysautonomia. Medical history included hypoparathyroidism and idiopathic cirrhosis. He did not have history of alcohol overuse, diabetes, or glucose intolerance. Examination revealed confluent hypopigmented macules in feet, vibratory sensation impairments up to knees, absent temperature sensation in feet, and abnormal Romberg test and tandem gait. Remainder of the neurological examination was normal. Laboratory tests were significant for elevated free kappa and lambda light chains, plasma VEGF levels twice over normal range, and an IgA monoclonal band on serum protein electrophoresis. Other relevant laboratory findings included PTH-independent hypercalcemia and alkaline phosphatase elevation. Radiographs of hands, elbows, shoulders, and knees disclosed non-sclerotic lytic lesions. Nerve conduction studies were consistent with a sensorimotor axonal polyneuropathy. The patient met diagnostic criteria for POEMS syndrome. Autologous stem cell transplantation was recommended but the patient declined. His vitiligo, neuropathy, and monoclonal gammopathy remain stable under surveillance at 4 years without pharmacotherapy. <h3>Conclusions:</h3> POEMS syndrome should be suspected in any patient with new onset of vitiligo in the presence of an underlying polyneuropathy and a monoclonal plasma cell proliferative disorder. <b>Disclosure:</b> Dr. Landman has nothing to disclose. Dr. Escobar-Montealegre has nothing to disclose. Dr. Singh has nothing to disclose. Dr. Morales has nothing to disclose. Dr. Rossi has nothing to disclose.

Plasma Markers for Early Prediction of Radiation-Induced Myocardial Damage.

There is no sensitive and effective method to predict radiation-induced myocardial damage (RIMD). The aim of this study was to explore effective plasma biomarkers for early prediction of RIMD after radiotherapy (RT) in lung cancer patients and in a rat model. Biomarker levels were measured in plasma samples collected before and after thoracic RT from 17 lung cancer patients. For the animal model, a single radiation dose of 40 Gy was delivered to the cardiac apex of female Wistar rats. Control rats received sham irradiation (0 Gy). Dynamic plasma biomarker detection and histopathological analysis to confirm RIMD were performed in rats up to 6 months after RT. In lung cancer patients, the plasma caspase-3 concentration was significantly increased after thoracic RT (P = 0.0479), with increasing but nonsignificant trends observed for caspase-1, CCL2, vascular endothelial growth factor (VEGF), interleukin-1β, and IL-6 (P > 0.05). Changes in caspase-3, VEGF, and IL-6 correlated significantly with mean heart dose (P < 0.05). In the RIMD rat model, caspase-1, caspase-3, CCl-2, VEGF, CCl-5, and TGF-β1 levels were significantly elevated in the first week post-RT (P < 0.05), which was earlier than pathological changes. Myocardial tissue of the RIMD rats also showed significant macrophage infiltration at 1 month (P < 0.01) and fibrosis at 6 months postradiation (P < 0.0001). Macrophage infiltration correlated significantly with plasma caspase-3, CCL2, CCL5, VEGF, and TGF-β1 levels from 3 weeks to 2 months post-RT. Increased plasma caspase-1, caspase-3, CCl-2, and VEGF levels were detected before RIMD-related pathological changes, indicating their clinical potential as biomarkers for early prediction of RIMD.

EFFECT OF BLOOD GLUCOSE CONTROL TOWARDS PLASMA AND VITREOUS LEVELS OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND PLACENTAL GROWTH FACTOR IN DIABETIC RATS

Purpose: To compare plasma and vitreous level of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in diabetic rats with poor blood glucose (BG) control, reconstitution of good BG control, and nondiabetic rats, and to investigate the effect of reconstitution of good BG control to VEGF and PlGF plasma and vitreous level. Methods: This is an experimental study using eighteen Sprague Dawley rats which were divided into intervention group (n=14) and control group (n=4). Intervention group were given Streptozotocin (STZ) injection to induce diabetes. After 4 weeks, intervention group was randomly divided into group I for termination and group II for reconstitution of good BG control with insulin for the following 4 weeks, and so was the control group. Plasma and vitreous samples were taken. VEGF and PlGF levels were evaluated with enzyme-linked immunosorbent assay (ELISA). Results: Seventeen of 18 rats survived in intervention group. BG level of intervention group II decreased dramatically to normoglycemia. ELISA at month 1 showed that VEGF vitreous level tend to be higher in intervention group I compared to control I, 196.36 ± 65.24 pg/dL and 123.64 ± 44.99, respectively (p=0.20). ELISA at month 2 showed that PlGF vitreous level of intervention group I were significantly higher compared to control I, 59.04 ± 2.48 and 51.93 ± 3.15, respectively (p=0.01). Vitreous and plasma VEGF of intervention group I and II were not different, while vitreous and plasma PlGF were significantly higher in group II. Conclusions: Vitreous levels of VEGF and PlGF were increased in diabetic rats compared to nondiabetic, and reconstitution of good BG control for 1 month were unable to reduce VEGF and PlGF levels.

Comprehensive assessment of the dynamics of angiogenesis in patients with psoriasis treated with methotrexate

Background. Evaluation of the severity of pathological angiogenesis in patients with psoriasis can be considered as a promising direction for monitoring the activity of the disease and the effectiveness of systemic therapy.&#x0D; Aims. Evaluation of interconnections between indicators of angiogenesis in the skin and nail bed of psoriasis patients with clinical characteristics of disease course and therapeutic response to the use of methotrexate by a comprehensive study of the morphometric data dynamics of videodermatoscopy in vascular bed of the skin, the severity of blood flow in the dermis and nail bed during ultrasonic power dopplerography and plasma concentrations of vascular endothelial growth factor (VEGF) and endothelin-1 (En-1).&#x0D; Materials and methods. Work is based on the data analysis from a survey of 82 patients with moderate to severe psoriasis vulgaris in the acute stage, who were first prescribed methotrexate in the form of subcutaneous injections at a dose of 1015 mg per week in combination with folic acid 5 mg per week. Before treatment and three months after the start of methotrexate therapy, all patients underwent videodermatoscopy with dimension of the density and size of dilated skin capillaries, ultrasonography of psoriatic plaques and nail bed of affected nails and measurement of doppler blood flow parameters and concentration of VEGF and En-1 in blood plasma.&#x0D; Results. A direct correlation was established between the average diameter of dilated skin capillaries (vascular glomeruli), the degree of increased blood flow in the doppler energy study of psoriatic plaques skin area and the plasma concentration of VEGF and En-1 and values of PASI, BSA, sPGA and DLQI indices, as well as the severity of doppler blood flow of the nail bed and NAPSI index (r = 0.210.73). Under the influence of methotrexate treatment, a decrease in diameter and density of vascular glomeruli (16.2 [12.9; 22.5] versus 25.2 [17.1; 33.7] m before treatment (p = 0.002) and (44.6 [31.6; 53.3] versus 53.5 [34.6; 67.4] before treatment (p = 0.04), respectively), the degree of blood flow in area of psoriatic plaques and the concentration of VEGF and En-1 (12.5 [6.7; 26.8] pg/ml versus 19.5 [4.7; 48.1] pg/ml after treatment (p = 0.002) and En-1 (168.2 [97; 319] versus 274.5 [146; 439] pg/ml(p = 0.003), respectively) was observed.&#x0D; Conclusions. Studied indicators of angiogenesis can be used as additional criteria for assessing the degree of activity and achieving clinical improvement/remission during systemic therapy in patients with moderate and severe psoriasis.

Clinical significance of plasma markers of angiogenesis in patients with psoriasis

BACKGROUND: Currently, many researchers attach great importance in psoriasis pathogenesis to hyperproduction of vascular endothelial growth factor (VEGF) and endothelin-1, which leads to increased angiogenesis in dermis and mediates processes of immune inflammation. At the same time, possibility of using these angiogenesis biomarkers as additional indicators of immune inflammation activity and disease activity has been poorly studied.&#x0D; AIMS: the purpose of the study was to assess the relationship between serum concentrations of VEGF and endothelin-1, structural changes in the capillary bed according to videodermatoscopy, and severity and prevalence of skin lesions in patients with psoriasis, duration of disease, presence of nail lesions, synovitis, enthesitis and spondylitis, as well as concomitant diseases of the cardiovascular system.&#x0D; MATERIALS AND METHODS: The work is based on examination data analysis of 132 patients with moderate and severe psoriasis vulgaris for the period 20202022. Patients were determined the levels of VEGF and endothelin-1 in blood plasma and underwent digital dermatoscopy to study the characteristics of angiogenesis vascular loci (vascular glomeruli) in the papillary dermis. All psoriasis patients with symptoms of musculoskeletal system lesions were examined by a rheumatologist, which was supplemented by ultrasonography of the joints.&#x0D; RESULTS: According to the results of enzyme immunoassay, it was found that the examined patients had an increased concentration of VEGF and endothelin-1 in blood plasma compared to the control group (respectively 19.5 [4.7; 48.1] pg/ml and 274.5 [146; 439] pg/ml versus 5.2 [0.5; 9.8] pg/ml and 96.5 [32; 188] pg/ml, p=0.004 and p=0.002). It was found that an increase in plasma concentrations of VEGF and endothelin-1 correlates with an increase in density of vascular glomeruli (respectively r=0.65 and r=0.74) and the average diameter of the glomerulus (respectively r=0.58 and r=0.56). A more pronounced increase in plasma concentrations of VEGF and endothelin-1 in patients with psoriasis was noted in patients with psoriatic arthritis and in the presence of synovitis. VEGF levels were higher in patients with severe psoriasis and in patients with nail lesions. Correlation analysis showed the strongest relationship between VEGF concentration and DAS28, DLQI, PASI and NAPSI values, as well as endothelin-1 concentration and PASI, BSA and DLQI values.&#x0D; CONCLUSIONS: The work showed that the plasma concentration of VEGF and endothelin-1 characterizes the degree of angiogenesis expression in the psoriasis pathogenesis, reflects morphology changes in capillaries of the affected skin, and can also be used as a marker of severe psoriasis and an increased risk of developing damage to the nails and synovial membranes of the joints.

Platelet-Rich Plasma Contains High Concentrations of DKK1, A Potent Inhibitor of Wnt Signaling that Limits Bone Regeneration and Hair Growth

Platelet-rich plasma (PRP) is a popular autologous therapy in the tissue regenerative technology space based on its enriched milieu of platelet-released growth factors (GFs), including platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). PRP is frequently used for hair restoration, wound healing, tendon and ligament repairs, and other soft-tissue settings, but PRP did not fulfill its original promise for enhancing bone grafts and bone augmentation in dentistry or orthopedics because it does not consistently promote osteogenesis. The effects of PRP on bone regeneration are often described as controversial, contradictory, and confusing, including evidence that greater platelet enrichment often leads to lesser osteogenic responses. The latter paradox suggests that limited PRP efficacy in bone regeneration may relate to platelet-derived factors that inhibit osteoblasts rather than inadequate GF concentrations. One candidate platelet-derived anti-osteogenic factor is Dickkopf-1 (DKK1), a potent soluble inhibitor of Wnt signaling that limits bone regeneration after bone damage. Recognizing that platelets store DKK1 in their alpha granules and rapidly release it upon platelet activation, we evaluated levels of DKK1, PDGF, and VEGF in human serum, plasma, platelet-poor plasma (PPP), and PRP. Sclerostin, another inhibitor of Wnt signaling that limits bone formation in undamaged bone, was also evaluated because platelets are not known to secrete sclerostin. We show that DKK1, PDGF, and VEGF concentrations are much higher in serum versus plasma, probably due to platelet activation during serum preparation. DKK1, PDGF, and VEGF concentrations were also higher in PRP versus plasma, and in plasma versus PPP. Activation of plasma or PRP with thrombin resulted in marked increases in DKK1, PDGF, and VEGF concentrations, with DKK1 levels in activated PRP being over 40-fold higher than the minimum concentration reported to inhibit osteogenesis in cell culture models. Conversely, sclerostin levels in plasma and PRP were unaffected by platelet activation and were significantly lower in serum versus standard plasma, providing new evidence that platelets do not secrete sclerostin. These results suggest that the beneficial effects of high GF levels in PRP may be limited by the presence of high levels of DKK1 released from the same platelet alpha granules.

Regulators of angiogenesis in chemotherapy-induced peripheral neuropathy

Background: Chemotherapy-induced peripheral polyneuropathy is a major neurotoxicity of treatment for acute lymphoblastic leukemia (ALL) in children. Pathophysiological mechanisms of the injury of peripheral neural system are not fully investigated; however, some studies have shown the involvement of vascular endothelial growth factors.&#x0D; Aim: To evaluate plasma levels of angiogenic growth factors in children with ALL and to identify their association with the development of vincristine-induced peripheral polyneuropathy.&#x0D; Materials and methods: This single center prospective study included 41 patients with ALL aged 3 to 17 years. All patients were given the ALL-MB 2015 chemotherapy regimen. Depending on the vincristine-induced peripheral polyneuropathy, the patients were divided into two groups: the main group (n = 22) comprised of the patients with neurological signs and symptoms of peripheral neuropathy and the control group (n = 19), those without clinical signs of the peripheral nervous system involvement. The levels of angiogenic growth factors (VEGF-A, VEGF-D, PlGF-1, and PDGF-BB) were measured in plasma by multiparameter immunofluorescent analysis.&#x0D; Results: During 3 months of the follow up the chemotherapy-induced signs of peripheral polyneuropathy developed in 53.6% (n = 22) of the children. In 72.7% (n = 16) of the patients the chemotherapy-induced peripheral polyneuropathy was characterized by a combination of neurologic abnormalities with prevailing motor symptoms. The comparative analysis of plasma angiogenic growth factors in children with ALL depending on the presence or absence of the vincristine-induced peripheral polyneuropathy showed that there was a significant decrease of the VEGF-A in those with chemotherapy-induced peripheral polyneuropathy, compared to those without (Me [Q1; Q3]: 178.20 [138.40; 228.45] and 558.50 [160.10; 650.0], respectively, p 0.017). This parameter had diagnostic sensitivity of 77.7% and specificity of 76.9%.&#x0D; Conclusion: We have shown a high clinical value of plasma vascular endothelial growth factor (VEGF-A) level, which makes it possible to consider it as a significant biological marker of neurotoxicity in vincristine-induced peripheral polyneuropathy.