Increased Vascular Endothelial Growth Factor Levels Research Articles

The effect of ACTH/MSH N-terminal fragment analogs on the anxiety level, pain sensitivity and levels of neurotrophic factors BDNF and VEGF in primary neuronal cultures of rats

ACTH/MSH-like peptides (melanocortins) have a wide range of neurotropic effects, including effects on learning and memory processes, neuroprotection, emotional state and pain sensitivity. Present work is aimed to compare the effects of peptides, the structure of which includes a natural fragment of ACTH and a stabilizing tripeptide PGP. The peptides ACTH4-7PGP (Semax), ACTH6-9PGP и ACTH7-10PGP were used in the work. The effects of these peptides on the exploratory behavior, anxiety level and pain sensitivity of white rats, as well as on the protein levels of the neurotrophic factors BDNF (brain derived neurotrophic factor) and VEGF (vascular endothelial growth factor) in primary neuron cultures were studied. A comparative study of the effects of analogs of different ACTH/MSH fragments revealed both similarities and differences in their neurotropic activity. The peptides structure of which includes a sequence of ACTH4-7 or ACTH6-9 have nootropic, anxiolytic and analgesic activity, and also cause an increase in VEGF levels in the culture of hippocampal neurons. The peptide containing the ACTH7-10 sequence in the structure exhibits anxiolytic activity, increases exploratory behavior, does not affect pain sensitivity and has a stimulating effect on BDNF and VEGF levels in neuronal cultures. The data obtained indicate that different parts of the N-terminal region of the ACTH molecule are responsible for the manifestation of certain neurotropic effects of melanocortins. The results of the study can be used in the development of therapeutics based on natural melanocortins.

Early activation of macrophage-2 with IL-4 in stromal vascular fraction increases VEGF levels and adipocyte count and maintains volume of fat graft in Wistar rats (Rattus norvegicus)

Several previous studies have demonstrated the benefits of early macrophage 2 activation fat grafts supplemented with macrophage culture. However, this approach is considered impractical in clinical settings because of intraperitoneal induction use. The aim of this study was to investigate the effect of early stromal vascular fraction (SVF) macrophage-2 activation with IL-4 on fat graft survival compared to SVF alone using an animal model for better fat graft viability. This experimental study included inguinal fat harvesting, isolated with collagenases to retrieve the SVF, and then injected with a combination of fat graft and SVF (0.3 mL) into the scalp region. The intervention group received an IL-4 intralesional injection on the third day, and the fat grafts were biopsied on days 7, 14, and 30. The primary outcomes were the final volume of the fat graft, vascular endothelial growth factor (VEGF) expression, and the adipocyte cell count using perilipin staining on immunohistochemistry examination. The group receiving IL-4 exhibited significantly higher VEGF on days 7, 14, and 30 (p=0.009, 0.009, and 0.021, respectively). Similarly, the IL-4 treatment significantly increased the perilipin concentration on days 7, 14, and 30 (p=0.008, 0.008, and 0.029, respectively). In this group, VEGF concentration was significantly increased on day 14 as compared to day 7 (p=0.009), while no significant difference was observed in the control group (p=0.090). Additionally, the IL-4 group displayed significantly less reduction of fat graft volume than the control group, as observed on days 7, 14, and 30 (p=0.009, 0.009, and 0.021, respectively). Overall, the study underscores the potential benefits of early M2 polarization in fat grafting, as well as providing practical advantages for improving fat graft volume retention.

Enhanced Brain Clearance of Tau and Amyloid-β in Alzheimer's Disease Patients by Transcranial Radiofrequency Wave Treatment: A Central Role of Vascular Endothelial Growth Factor (VEGF).

While drainage/removal of fluid and toxins from the brain by cerebrospinal fluid (CSF) directly into venous blood is well-known, a second drainage route has recently been (re)discovered-meningeal lymphatic vessels (mLVs)-which are responsible for up to half of total brain fluid/toxin drainage. The cytokine vascular endothelial growth factor (VEGF) increases mLV diameter and numbers to increase mLV drainage, resulting in increased mLV drainage. Alzheimer's disease (AD) is characterized by low plasma and CSF levels of VEGF. To determine if non-invasive transcranial radiofrequency wave treatment (TRFT), through modulation of VEGF levels in blood and CSF, can affect removal of toxins tau and amyloid-β (Aβ) from the brain. Eight mild/moderate AD subjects were given twice-daily 1-hour TRFT sessions at home by their caregivers. Blood and CSF samples were taken at baseline and following completion of 2 months of TRFT. In plasma and/or CSF, strong baseline correlations between VEGF levels and AD markers (t-tau, p-tau, Aβ1-40, Aβ1-42) were eliminated by TRFT. This effect was primarily due to TRFT-induced increases in VEGF levels in AD subjects with low or unmeasurable "baseline" VEGF levels. These increased VEGF levels were associated with increased clearance/drainage of tau and Aβ from the brain, likely through VEGF's actions on mLVs. A new mechanism of TRFT is identified (facilitation of brain tau and Aβ clearance via VEGF) that is likely contributory to TRFT's reversal of cognitive impairment in AD subjects. TRFT may be particularly effective for cognitive benefit in AD subjects who have low VEGF levels.

VEGF expression disparities in brainstem motor neurons of the SOD1G93A ALS model: Correlations with neuronal vulnerability

Amyotrophic lateral sclerosis (ALS) is a rare neuromuscular disease characterized by severe muscle weakness mainly due to degeneration and death of motor neurons. A peculiarity of the neurodegenerative processes is the variable susceptibility among distinct neuronal populations, exemplified by the contrasting resilience of motor neurons innervating the ocular motor system and the more vulnerable facial and hypoglossal motor neurons. The crucial role of vascular endothelial growth factor (VEGF) as a neuroprotective factor in the nervous system is well-established since a deficit of VEGF has been related to motoneuronal degeneration. In this study, we investigated the survival of ocular, facial, and hypoglossal motor neurons utilizing the murine SOD1G93A ALS model at various stages of the disease. Our primary objective was to determine whether the survival of the different brainstem motor neurons was linked to disparate VEGF expression levels in resilient and susceptible motor neurons throughout neurodegeneration. Our findings revealed a selective loss of motor neurons exclusively within the vulnerable nuclei. Furthermore, a significantly higher level of VEGF was detected in the more resistant motor neurons, the extraocular ones. We also examined whether TDP-43 dynamics in the brainstem motor neuron of SOD mice was altered. Our data suggests that the increased VEGF levels observed in extraocular motor neurons may potentially underlie their resistance during the neurodegenerative processes in ALS in a TDP-43-independent manner. Our work might help to better understand the underlying mechanisms of selective vulnerability of motor neurons in ALS.

The effect of curcumin on on intravitreal proinflammatory cytokines, oxidative stress markers, and vascular endothelial growth factor in an experimental model of diabetic retinopathy.

The prevalence of diabetic retinopathy (DR) is high among individuals with diabetes. Curcumin (CUR) has been suggested as a possible treatment for this condition. This study aimed to investigate the impact of CUR on pro-inflammatory cytokines, oxidative stress markers, and vascular endothelial growth factor (VEGF) in an experimental model of DR. The study used Spontaneously Diabetic Torii (SDT) rats and divided them into groups to receive various CUR doses (10, 50, 100 mg/kg/day) or distilled water for four weeks. Non-diabetic Sprague-Dawley (SD) rats were used as a control group. Pro-inflammatory cytokines (interleukin (IL)-1, IL-6, tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ)) (by ELISA), oxidative stress markers (superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GPX), catalase (CAT)), and VEGF expression (by RT-PCR) and content (by Western-blot and immunostaining) were assessed as outcome measures. The study found that diabetic rats who received varying doses of CUR showed a decrease in pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1), oxidative stress markers (SOD, MDA, GPX, CAT), and VEGF expression and content in the vitreous. The decrease in these markers was dose-dependent and significantly different from diabetic rats who did not receive CUR (p<0.01). However, there was no significant difference in the vitreous level of IL-6 between the groups (p=0.35). The study concluded that CUR has the potential to alleviate inflammation and oxidative stress induced by diabetes in the vitreous microenvironment of rats. CUR also reduced the increase in VEGF levels in the vitreous of diabetic rats. These findings suggest that CUR could be a viable therapeutic option for the treatment of DR.

Effectiveness of Sucralphate and Platelet-Rich Plasma Combinations For Vascular Endothelial Growth Factor (VEGF) Expression In Diabetic Ulcer Healing

Background: Diabetic ulcer is one of the most feared chronic infections due to Diabetes Mellitus because it can lead to amputation and death. Aim: To prove the effectiveness of sucralfate and platelet-rich plasma (PRP) combination for Vascular Endothelial Growth Factor (VEGF) expression in diabetic ulcer healing. Methods: This research is an experimental study of Phase I Clinical Trial with post-test only group design. There were 20 patients with diabetic ulcers divided into two groups, namely the treated group that was given sucralfate and PRP therapy and the control group was given standard therapy of normal saline drainage and gauze covered. Parameters were VEGF expression levels, wound area after being given therapy, and side effect from the treatment. Data on VEGF expression levels were obtained by means of examination with the Quantikine Human VEGF-ELISA Quantikine, R&amp;D System, Inc, Minneapolis. The measurement of the wound area was assessed based on several criteria, namely grade 0 (no change), grade 1 (wound size reduced to less than of the previous wound), grade 2 (wound size was reduced to less than of the previous wound, but granulation was visible), and grade 3 (wound has closed completely). Result: In unpaired t-test, the mean VEGF expression was 98.18+10.96 in the treatment group and 66.69+23.79 in the control group which showed significant difference in VEGF expression levels (p = 0.003). In Mann-Whitney test, the mean wound area was 0.68+0.40 in the treatment group and 0.77+0.67 in the control group which showed that there was not any significant difference in wound area (p = 0.152). There were no side effects in both study group. Conclusions: The combination of sucralfate and PRP can increase VEGF levels significantly in diabetic ulcer patients but does not show a different effect in reducing wound area compared to standard treatment. The combination did not cause any side effects in the study subjects, as well as those using standard treatment.

Serum angioneurin levels following electroconvulsive therapy for mood disorders.

The efficacy of electroconvulsive therapy (ECT) in treating mood disorders (MDs) is hypothesized to be mediated by the induction of neurotrophic factors (denoted "angioneurins") that trigger neuronal plasticity. This study aimed to assess the effects of ECT on serum angioneurin levels in patients with MD. A total of 110 patients with MDs including 30 with unipolar depression, 25 with bipolar depression (BD), 55 with bipolar mania (BM), and 50 healthy controls were included in the study. Patients were subdivided into two groups: those who received ECT + medication (12 ECT sessions) and those who received only medication (no-ECT). Depressive and manic symptom assessments and measurements of vascular endothelial growth factor (VEGF), fibroblast growth factor-2, nerve growth factor (NGF), and insulin-like growth factor-1 levels in blood samples were performed at baseline and week 8. Patients in the ECT group, specifically those with BD and BM, had significantly increased levels of VEGF compared to their baseline VEGF levels (p=0.002). No significant changes in angioneurin levels were observed in the no-ECT group. Serum NGF levels were significantly associated with a reduction in depressive symptoms. Angioneurin levels were not associated with manic symptom reduction. This study hints that ECT may increase VEGF levels with angiogenic mechanisms that amplify NGF signaling to promote neurogenesis. It may also contribute to changes in brain function and emotional regulation. However, further animal experiments and clinical validation are needed.

Study of single nucleotide polymorphism of vascular endothelium factor in patients with differentiated thyroid cancer

BackgroundGenetic alterations and high levels of the vascular endothelial growth factor (VEGF) are presumptive risk factors for differentiated thyroid cancer (DTC).ObjectiveThis work aims to study the presence of − 634G/C polymorphism of vascular endothelial growth factor (rs2010963) and its’ serum level in patients with DTC and comparing these results with those of the control subjects.Material and methodThe study was a retrograde case–control study that included seventy patients with DTCin addition to seventy apparently healthy control subjects. Blood sample was taken and subjected to study of − 634G/C VEGF polymorphism (rs2010963) by real time PCR and measurement of its’ plasma level by immunoassay kit (ELISA).ResultsRegarding genotyping of VEGFA − 634G/C (rs2010963) polymorphism, there was significant increase in CG and GG genotypes (28.6%, 18.6% respectively) among patients compared to control subjects (20.0%, 4.3% respectively) and significant increase in CC genotype in control subjects (75.7%) compared to patients (52.9%), P = 0.001. The VEGF mean ± SD level was significantly elevated in patients compared to control subjects (1215.81 ± 225.78 versus 307.16 ± 91.81, P = 0.006). Moreover, there was significant increase in VEGF levels in patients with CG and GG genotypes (1295.9 ± 68.74, 1533.08 ± 109.95, respectively) compared to patients with CC genotype (1061 163.25), P = 0.001).ConclusionThere was significant increase in GG and CG genotypes in patients with DTC compared to control subjects which may suggest a predisposing role for these genotypes in development of DTC. Moreover, there was significant increase in serum level of vascular endothelial growth factor in patients with GG and CG genotypes which may reflect the mechanism of these genotypes in development of DTC.

Amfenac together with simvastatin reduces IL‐8 and MCP‐1 and increases VEGF release from ARPE‐19 cells upon inflammatory conditions

AbstractPurpose: Rhegmatogenous retinal detachment (RRD) is a sight‐threatening condition with the separation of the neurosensory retina from the retinal pigment epithelium (RPE). Clinical data have associated statin medication with lower risk of re‐vitrectomy in patients operated for RRD. We have previously shown statins to have anti‐inflammatory properties in lipopolysaccharide (LPS)‐treated RPE cells. The purpose of the present study was to examine whether the nonsteroidal anti‐inflammatory drug (NSAID) amfenac could complement the anti‐inflammatory effect of simvastatin in human RPE cells under pathophysiological conditions induced by IL‐1a. In addition to inflammatory markers, we studied the effects of amfenac and simvastatin on growth factors regulating blood vessel formation.Methods: ARPE‐19 cells were pre‐treated with 0.1 μM amfenac and 5 μM simvastatin for 24 h after which 10 pg/ml of IL‐1α was added for 24 h. Enzyme‐linked immunosorbent assay (ELISA) was used to measure secretion of cytokines (IL‐8, MCP‐1), vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF). Cytotoxicity was measured using the lactate dehydrogenase (LDH) assay.Results: Amfenac and simvastatin were well tolerated upon inflammatory conditions. Both medicines alone and together reduced IL‐1a‐activated IL‐8 release. Simvastatin significantly reduced also the release of MCP‐1. The effect of amfenac alone was not significant but together with simvastatin, significant reduction in MCP‐1 levels was still reached. IL‐1a with the DMSO solvent increased release of PEDF and VEGF compared to DMSO group. Exposure of IL‐1α‐treated cells to amfenac and simvastatin together increased VEGF levels with no changes in the PEDF.Conclusions: Amfenac and simvastatin showed potential to reduce inflammation in the retina upon retinal detachment. Increased VEGF levels may have neuroprotective effects by improving connections between RPE cells and photoreceptors.

Vascular endothelial growth factor and the risk of venous thromboembolism: a genetic correlation and two-sample Mendelian randomization study

BackgroundThe relationship between vascular endothelial growth factor (VEGF) and the risk of venous thromboembolism (VTE) has always been one of the concerns in the medical field. However, the causal inferences from published observational studies on this issue may be affected by confounders or reverse causality. We performed a two-sample bidirectional Mendelian randomization (MR) to infer the associations between VEGF and VTE.MethodsSummary statistics from genome-wide association studies (GWAS) for VEGF and VTE were obtained from published meta-analysis studies and the FinnGen consortium, respectively. Independent genetic variables significantly associated with exposure were selected as instrumental variables. Linkage disequilibrium score regression (LDSC) and five robust MR analytical approaches were conducted to estimate the genetic correlations and causal inference. The MR-Egger intercept, Cochran’s Q, and MR pleiotropy residual sum and outlier (MR-PRESSO) were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on outcomes. Notably, replication analyses were performed using different subgroups of VTE.ResultsLDSC failed to identify genetic correlations between VEGF and VTE. Based on 9 SNPs, the circulating VEGF level was positively related to the risk of VTE using inverse variance weighting (IVW) method (odds ratio (OR) = 1.064, 95% confidence interval (CI), 1.009–1.122). Reverse MR analyses showed that genetic liability for VTE was not associated with increased VEGF level (β = -0.021, 95% CI, -0.087-0.045). Pleiotropy-robust methods indicated no bias in any estimates.ConclusionsOur findings failed to detect coheritability between VEGF and VTE. The suggestive positive effect of the higher VEGF level on the VTE risk may have clinical implications, suggesting that VEGF as a possible predictor and therapeutic target for VTE prevention need to be further warranted.

Association of Serum Fibrinogen and Plasma VEGF Levels with Tumor Characteristics and Treatment Response in Operable Breast Carcinoma

A search for factors predicting the behavior of the tumor, its invasiveness, metastasis, response to treatment, and prognosis is the primary focus of breast cancer research. The objective of the present study was to study the association of fibrinogen and vascular endothelial growth factor (VEGF) with various parameters of breast carcinoma. A case control was conducted in which fibrinogen, and VEGF levels were compared between cases and controls and also with various characteristics of breast carcinoma such as T stage, lymph node positivity, grade, lymphovascular invasion, and receptor status. The effect of surgery of breast cancer on fibrinogen and VEGF levels was also studied. The levels of fibrinogen and VEGF were significantly higher in cases when compared to controls (p < 0.001). Increased fibrinogen level was significantly associated with higher grade of the tumor, lymph node metastasis, and lymphovascular invasion. Increased VEGF level was significantly associated with higher grade and lymphovascular invasion of the tumor. After treatment, there was a statistically significant fall in the levels of the above mediators (p < 0.001). Serum fibrinogen and plasma VEGF levels were significantly higher in patients of breast carcinoma and had significant association with invasiveness of the tumor.

Modulatory Effects of Swimming Training on Hypoxia-Induced Factors in Heart Tissue of Rats Exposed to Chronic Stress

Background: Monitoring cardiac, metabolic, neurological, and aging responses to stressors is critical. This study aimed to investigate the effect of swimming training on HIF-1α and vascular endothelial growth factor (VEGF) levels in heart tissue of rats exposed to chronic stress. Methods: To this end, 30 male Wistar rats (age: 10 - 12 weeks, weight: 220 ± 20 g) were randomly divided into five equal groups of six rats as follows: (1) Con (no treatment for 10 weeks); (2) CS + ST (4 weeks of stress, 4 weeks of swimming); (3) ST (4 weeks of swimming); (4) CS (4 weeks of stress); (5) CS-time (4 weeks of stress, 6 weeks of no treatment). Anxiety-like behaviors were measured by an open field test. Heart tissue was immunohistochemically assessed for HIF-1α expression using a polyclonal antibody. Vascular endothelial growth factor protein levels were also determined using western blot analysis. To analyze the data, Kolmogorov-Smirnov, One-way ANOVA, and Tukey’s post hoc tests were used, and P ≤ 0.05 was considered statistically significant. Results: The results showed that chronic mild stress (CMS) significantly decreased the HIF-1α expression in heart tissue in CS and CS-time groups (P &lt; 0.05). Furthermore, the result revealed that swimming training significantly increased the level of HIF-1α expression in heart tissue in ST and CS + ST groups (P &lt; 0.05). Although swimming training increased HIF-1α levels in the CS + ST group after a period of four weeks of CMS, these increases were smaller than those observed in ST and control groups (P &lt; 0.05). The results from the One-way ANOVA test also demonstrated that the CMS significantly downregulated the VEGF expression in heart tissue in CS and CS-time groups, whereas swimming training significantly increased its level in ST and CS + ST groups (P &lt; 0.05). Although swimming training increased VEGF levels in the CS + ST group after a period of four weeks of CMS, these increases were smaller than those detected in ST and control groups. Conclusions: Although chronic mild stress had the potential to reduce hypoxia-induced factors in heart tissue, swimming training modified these factors.

99. Aging Associated Loss of Vegfa Impairs Muscle Regeneration

Purpose: Global populations, particularly in developed countries, have continued to age. Notably, aging is intimately correlated with frailty, a parameter that has been previously demonstrated to correlate significantly with mortality and concomitantly correlate with loss of muscle mass. The molecular mechanisms behind aging associated impaired skeletal muscle regeneration remain incompletely understood. Our group previously demonstrated aging-associated loss of hypoxia signaling impairs skeletal muscle myogenic potential. Given these findings, we hypothesized vascular endothelial growth factor (VEGFA), a potent downstream signal well characterized in nascent vascular ingrowth and muscle progenitor differentiation, to critically regulate regeneration in young and aged skeletal muscle. Methods: Young C57BL/6 mice (12-14 weeks old) and old C57BL/6 mice (24-25 months old) were subjected to a previously validated model of muscle cryoinjury (n=5-6/group) to induce regeneration. The tibialis anterior muscle was injured using direct contact with a metal probe cooled in dry ice. Quantifications of cross sectional area (CSA) of myofibers were performed across 10 photos/sample by blinded reviewer via ImageJ. Western blots were performed from whole TA muscle lysates for quantification of VEGFA with GAPDH for normalization. To evaluate the role of VEGF in muscle regeneration, we performed a similar and separate series of experiments using VEGFlo (Jackson Labs Stock No. 027315) mice, which exhibit a systemic, 75% decrease in VEGFA activity, and littermate controls. In addition, ML228, a hypoxia signaling activator known to increase VEGFA levels, was injected into both young and old mice, as well as VEGFlo and littermate controls, to determine whether VEGFA augmentation promotes muscle regeneration in aging. Results: Old mice demonstrated markedly impaired ability of regenerating myofiber CSA on days post injury (DPI) 5 in comparison to young mice (Young vs. Old: 526 vs. 373µm2, p<.001) and DPI 10 (Y v. O: 1250 vs. 833µm2, p<.001). VEGFA protein levels were markedly reduced in the gastrocnemius of old mice in comparison to young. Similarly, VEGFlo mice exhibited significantly smaller CSA of regenerating fibers as compared to littermate controls (WT vs. lo: 541 vs. 238µm2, p=.0011). Pharmacologic augmentation of VEGFA, using ML228, improved skeletal muscle regeneration in both old mice and VEGFlo mice. (WT vs. lo: CSA 757 vs. 662µm2, p=.387). Conclusions: Muscle regeneration declines with with aging, in a fashion correlated to loss of VEGFA levels within skeletal muscle. Systemic loss of VEGFA is further correlated with poor muscle regeneration in genetically modified mice. Furthermore, exogenous activation of hypoxic signaling/VEGFA reverses this reduced capacity for muscle regeneration in old and VEGFlo mice. Supplementation of VEGFA could represent a therapeutic target in aging patients with skeletal muscle loss.

Subclinical Hypothyroidism in Patients with Diabetic Retinopathy: Role of Vascular Endothelial Growth Factor.

This study was conducted by considering the vital role of Vascular Endothelial Growth Factor (VEGF) in the development of Diabetic Retinopathy (DR) on the one hand and the frequent association between Subclinical Hypothyroidism (SCH) and DR on the other hand. The present study was proposed to explore the possible role of VEGF in the relation between SCH and DR; thus, we investigated the relationship between SCH and VEGF levels in patients with DR. Two hundred patients with DR were recruited in this study [100 patients with Proliferative Diabetic Retinopathy (PDR) and 100 patients with Non-Proliferative Diabetic Retinopathy (NPDR)]. Patients with DR were divided into 2 groups according to thyroid function, patients with SCH or those with euthyroidism. Patients were subjected to careful history taking and underwent clinical and ophthalmological examination. Fasting blood glucose, glycosylated hemoglobin, fasting insulin, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), TSH, FT4, FT3, VEGF, and thyroid volume were assessed. Among all the studied patients, 21.5% (43/200) had SCH. DR patients with SCH had older age, longer diabetes duration, and higher HbA1c, HOMA-IR, and VEGF than those with euthyroidism. The frequency of PDR in patients with SCH was 72.1% (31/43) and 43.9% (69/157) in those with euthyroidism, whereas the frequency of NPDR in patients with SCH was 27.9 (12/43) and 56.1% (88/157) in those with euthyroidism (P 0.003). In multivariate analysis, PDR, HOMA- IR, and VEGF levels were the significant predictor variables of SCH. Increased VEGF levels may be implicated in the relationship between SCH and DR.

Beneficial Effects of Caffeic Acid Phenethyl Ester on Wound Healing in a Diabetic Mouse: Role of VEGF and NO

Cutaneous wound healing is delayed in patients with diabetes. Caffeic acid phenethyl ester (CAPE) has been identified as an effective constituent of propolis with improved wound healing abilities via an oxidative stress decrease. However, its impact on wound healing in diabetic models and its underlying mechanisms remain unclear. Determining the vascular endothelial growth factor (VEGF) contents in a human vascular smooth muscle cell (VSMC)-conditioned medium was assessed using human VEGF immunoassay and vascular reactivity using porcine coronary artery rings. Later, C57BL/6 or db/db mice were anesthetized, after which a 6-mm biopsy punch was manipulated for perforation via the back skin. Subsequently, CAPE was applied to the wound and changed daily. Furthermore, the injury in each mouse was digitally photographed, and the wound area was quantified. We observed that CAPE increased VEGF levels in human VSMC-conditioned medium, improved endothelium-dependent nitric oxide (NO)-mediated vasorelaxation, inhibited U46619-induced vasoconstriction porcine coronary artery, and enhanced cutaneous wound healing in the diabetic mouse model. Hence, we propose that CAPE improves wound healing in diabetic mice, which is aided by increased VEGF and NO expression.

Membrane progesterone receptor \u03b1 (mPR\u03b1) enhances hypoxia-induced vascular endothelial growth factor secretion and angiogenesis in lung adenocarcinoma through STAT3 signaling

Lung cancer remains a huge challenge to public health because of its high incidence and mortality, and lung adenocarcinoma (LUAD) is the main subtype of lung cancer. Hypoxia-induced vascular endothelial growth factor (VEGF) release and angiogenesis have been regarded as critical events in LUAD carcinogenesis. In the present study, membrane progesterone receptor α (mPRα) is deregulated within LUAD tissue samples; increased mPRα contributes to a higher microvessel density (MVD) in LUAD tissues. mPRα knockdown in A549 and PC-9 cells significantly inhibited STAT3 phosphorylation, as well as HIF1α and VEGF protein levels, decreasing cancer cell migration and invasion. The in vivo xenograft model further confirmed that mPRα enhanced the aggressiveness of LUAD cells. Furthermore, mPRα knockdown significantly inhibited hypoxia-induced upregulation in HIF1α and VEGF levels, as well as LUAD cell migration and invasion. Under the hypoxic condition, conditioned medium (CM) derived from mPRα knockdown A549 cells, namely si-mPRα-CM, significantly inhibited HUVEC migration and tube formation and decreased VEGF level in the culture medium. In contrast, CM derived from mPRα-overexpressing A549 cells, namely mPRα-CM, further enhanced HUVEC migration and tube formation and increased VEGF level under hypoxia, which was partially reversed by STAT3 inhibitor Stattic. In conclusion, in LUAD cells, highly expressed mPRα enhances the activation of cAMP/JAK/STAT3 signaling and increases HIF1α-induced VEGF secretion into the tumor microenvironment, promoting HUVEC migration and tube formation under hypoxia.

Novel sulfonamide-chalcone hybrid stimulates inflammation, angiogenesis and upregulates vascular endothelial growth factor (VEGF) in vivo.

Chalcones and sulfonamides are well-known chemical groups associated with several biological activities such as antibiotic, anti-inflammatory, and antitumor activities. Over the past few decades, a series of sulfonamide-chalcone hybrids have been synthesized and assessed to develop compounds with interesting biological properties for application in disease therapy. In the present study, a new sulfonamide-chalcone hybrid μ - (2,5-dichloro-N-{4-[(3E)-4-(3-nitrophenyl) buta-1,3-dien-2-yl] phenyl} benzene sulfonamide), or simply CL185, was synthesized, and its angiogenic activity was assessed using the chick embryo chorioallantoic membrane (CAM) assay at different concentrations (12.5, 25, and 50μg/μL). To further investigate the role of CL185 in the angiogenic process, we evaluated the levels of vascular endothelial growth factor (VEGF) in all treated CAMs. The results showed that all concentrations of CL185 significantly increased tissue vascularization (p<0.05) as well as the parameters associated with angiogenesis, in which inflammation was the most marked phenomenon observed. In all CAMs treated with CL185, VEGF levels were significantly higher than those in the negative control (p<0.05), and at the highest concentration, VEGF levels were even higher than in the positive control (p<0.05). The pronounced angiogenic activity displayed by CL185 may be related to the increase in VEGF levels that were stimulated by inflammatory processes observed in our study. Therefore, CL185 presents a favorable profile for the development of drugs that can be used in pro-angiogenic and tissue repair therapies.

Evaluation of 8 Weeks of Different Muscle Tensions on Some MicroRNAs Related to Angiogenesis of Muscular Hypertrophy of Bodybuilders

Background and Aim: Angiogenesis is the most important foundation of exercise-induced hypertrophy. This study aimed to investigate the effect of 8 weeks of different muscle tension training on some microRNAs related to angiogenesis and muscle hypertrophy in bodybuilders. Materials and Methods: The present study is a quasi-experimental study with a pre-test-post-test design. The study groups included resistance training group 1 (10 people), resistance training group 2 (10 people), and the control group (10 people). The study subjects were selected from male bodybuilders who have done regular training for at least three years and are aged between 25 and 30 years. The study was explained to them, and 48 hours before and after the test, 5 mL of blood was taken from each sample. Descriptive statistics, including Mean±SD, charts and tables, and inferential statistics, including analysis of variance (ANOVA) and post hoc test, were performed using SPSS software. First, the Kolmogorov-Smirnov test was used to determine the normality of the data. Then, to compare the differences between the groups, the ANOVA was used, and if it was significant, the Bonferroni post hoc test was used. Results: This study showed that resistance groups 1 and 2 significantly increased miR-1 in bodybuilders. Also, group 1 had a greater effect than resistance group 2. The results showed that resistance training in different time points and sets had different effects on molecular pathways of hypertrophy. So, two hours after resistance training, mir-1 levels did not increase significantly, but 4 hours after resistance training, the levels of these microRNAs increased. This study showed that group 1 had a more significant effect on miR-206 levels than resistance group 2. Conclusion: The results of this study indicated that resistance training significantly increases the vascular endothelial growth factor (VEGF) levels of bodybuilders. Also, the results showed that in group 2, an increase in VEGF levels led to a greater effect on angiogenesis in these samples.

The Effect of Hypoxia Inducible Factor -1 Alpha and Vascular Endothelial Growth Factor Level in Type 2 Diabetes Microvascular Complications and Development.

Background:Angiogenesis in diabetic patients is often caused by hyperglycemia induced by hypoxiaObjective:The aim of this study was to analyze the serum level of Hypoxia Inducible Factor -1α (HIF-1α) and Vascular Endothelial Growth Factor (VEGF) between March until Desember 2020.Methods:This is a cross-sectional analytic methods, 135 patients with Type 2 Diabetes 48 samples with Microvascular complication and 87 samples with non-microvascular complication were recruited from the various primary health care centers in Medan city and surrounding areas in North Sumatera. VEGF levels and HIF-1α tested were done with ELISA methods in the laboratory of Medical Faculty, Universitas Sumatera Utara. Statistical analysis was performed using the IBM SPSS Statistics version 24. The significance level was set up to 0.005.Results:The median HIF-1 levels in patients with microvascular complications were lower than those without microvascular complications, with a range of HIF-1α values in non-complicated samples (0.02-13.96) ng/ml and a range of HIF-1α values in vascular complications (0.52- 8.87) mg/dL. There was a significant difference in HIF-1α levels in patients with Type-2 DM with complications compared to those without complications (p<0.05). Median VEGF levels were higher in complicated Type-2 DM. There was no difference in VEGF levels in patients with Type-2 DM with complications compared to those without complications (p > 0.005).Conclusion:HIF-1α and VEGF levels showed the development in vascularity. With the higher level of HIF-1α, an increase in VEGF levels were found, indicating the angiogenesis is occurring. Although complications have not yet occurred, it is predicted that high VEGF values will cause vascular complications in the future.

Butylphthalide Combined With Conventional Treatment Attenuates MMP-9 Levels and Increases VEGF Levels in Patients With Stroke: A Prospective Cohort Study.

Background and Purpose: Butylphtalide increases the vascular endothelial growth factor (VEGF) and decreases matrix metalloproteinase (MMP)-9 in animal models of stroke and might be of use in the management of stroke. To explore whether butylphthalide combined with conventional treatment can change the levels of MMP-9 and VEGF and the National Institutes of Health Stroke Scale (NIHSS) scores of patients with stroke.Methods: This was a prospective cohort study involving inpatients admitted to the Jiangxi Provincial People's Hospital (January–June 2019) due to acute cerebral infarction. The patients received conventional treatments with or without butylphthalide. The changes in the NIHSS scores were compared between groups. Plasma MMP-9 and VEGF were measured by enzyme-linked immunosorbent assay.Results: A total of 24 patients were included in the conventional treatment group and 46 in the butylphthalide group. The butylphthalide group showed lower MMP-9 (130 ± 59 vs. 188 ± 65, p = 0.001) and higher VEGF (441 ± 121 vs. 378 ± 70, p = 0.034) levels on day 6 compared with the conventional treatment group. The changes in MMP-9 and VEGF were significant, starting on day 3 in the butylphthalide group but on day 6 in the conventional treatment group. There were no differences between the two groups in the NIHSS scores at admission and at discharge (p > 0.05). The overall response rate was higher in the butylphthalide group compared with the conventional treatment group (63.0 vs. 37.5%, p = 0.042).Conclusion: Butylphthalide combined with conventional treatment can decrease MMP-9 levels and increase VEGF levels. The patients showed the reduced NIHSS scores, possibly suggesting some improvement in prognosis after stroke. Still, the conclusions need to be confirmed in a larger sample and in different etiological subtypes of stroke.