Peripheral Vascular Endothelial Growth Factor Research Articles

Correlation between peripheral blood α1-MG, DNMT1 expression, and the severity of diabetic nephropathy renal pathological damage.

To explore the correlation between peripheral blood α1-microglobulin (α1-MG) and monocyte DNA methyltransferase 1 (DNMT1) expression and the severity of renal pathological damage in diabetic nephropathy (DN). The study group comprised 100 patients with DN who underwent treatment at our hospital from January 2022 to January 2023, while the control group consisted of 50 patients with uncomplicated diabetes. The relative expression levels of peripheral blood α1-MG and DNMT1 were compared between the 2 groups of patients. Additionally, the levels of vascular endothelial growth factor (VEGF) were measured, and the diagnostic value of DN was explored using ROC curves. Furthermore, the correlation between the aforementioned indicators and the severity of renal pathological damage in the patients of the study group was analyzed. Compared to the patients in the control group, the patients in the study group showed increased relative expression levels of peripheral blood α1-MG and DNMT1, as well as elevated levels of VEGF (P < .05). The diagnostic value of peripheral blood α1-MG, DNMT1 relative expression levels, and VEGF levels for DN was explored using ROC curves. The AUC values were 0.907, 0.923, and 0.936, respectively (P < .05). The relative expression levels of peripheral blood α1-MG, DNMT1, and VEGF levels in DN patients increase with the elevation of the interstitial fibrosis and tubular atrophy scoring (IFTA) score, showing a positive correlation with r-values of 0.651, 0.710, and 0.628, respectively (P < .05). The relative expression levels of peripheral blood α1-MG, DNMT1, and VEGF levels in DN patients increase with the elevation of the interstitial inflammation score, showing a positive correlation with r-values of 0.771, 0.633, and 0.678, respectively (P < .05). The relative expression levels of peripheral blood α1-MG, DNMT1, and VEGF levels in DN patients increase with the elevation of the glomerular grading, showing a positive correlation with r-values of 0.714, 0.609, and 0.677, respectively (P < .05). The expression levels of peripheral blood α1-MG, DNMT1, and VEGF are significantly elevated in patients with DN. These levels show a positive correlation with the IFTA score, interstitial inflammation score, and glomerular grading, contributing to the diagnosis and assessment of DN.

Effects of Resistance Exercise on Neuroprotective Factors in Middle and Late Life: A Systematic Review and Meta-Analysis.

Neuroprotective factors are involved in brain functioning. Although physical exercise has been shown to have a positive influence on these factors, the effect of resistance exercise on them is not well known. This systematic review and meta-analysis aimed to 1) estimate the efficacy of resistance exercise on major neuroprotective factors, such as insulin-like growth factor-1 (IGF-1), brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF), in middle and late life and 2) determine whether the effect is dose dependent. A systematic search was conducted in CINAHL, Cochrane CENTRAL, MEDLINE, Scopus, PEDro, SPORTDiscus, and Web of Science up to November 2022. Random effects models were used to estimate standardized mean differences (SMDs) and their respective 95% confidence intervals (CI) for the effect of resistance exercise on peripheral IGF-1, BDNF or VEGF levels in older adults. Thirty randomized clinical trials with 1247 subjects (53.25% women, 45-92 years) were included in the systematic review, and 27 were selected for the meta-analysis. A significant effect of resistance exercise on IGF-1 levels was observed (SMD: 0.48; 95% CI: 0.27, 0.69), being more effective when performing 3 sessions/week (SMD: 0.55; 95% CI: 0.31, 0.79) but not on BDNF (SMD: 0.33; 95% CI: -0.29, 0.94). The effect on VEGF could not be determined due to the scarcity of studies. Our data support the resistance training recommendation in middle and late life, at a frequency of at least 3 sessions/week, to mitigate the neurological and cognitive consequences associated with aging, mainly through IGF-1.

What is the link between the antidepressants, the transcranial magnetic stimulation and the peripheral vascular endothelial growth factor?

IntroductionVascular endothelial growth factor (VEGF) has been implicated in mediating the effect of antidepressants (AD) and electroconvulsive therapy on depression since it plays a significant role in the neurogenesis. However, the serum VEGF level has not been investigated so far in association with rTMS treatment in patients with major depressive disorder (MDD).ObjectivesThe aim of our study was to compare the effect of the antidepressants and of the repetitive transcranial magnetic stimulation on the serum vascular endothelial growth factor and its association with the responsiveness to the treatments.MethodsA dataset of 50 patients with TRD who were treated with AD (n=33) and bilateral rTMS for 2x5 days (n=17) was analysed (sample ’rTMS&amp;AD’). Montgomery-Asberg Depression Scale (MADRS) was used for monitoring the symptom changes. The serum VEGF levels and symptoms were assessed on the first (V1), on the 14th (V2) and on the 28th day (V3). The VEGF levels were measured by ELISA assay.ResultsThe baseline VEGF levels were significantly higher in non-responders both in the rTMS&amp;AD (p=0.04) and AD samples (p=0.02) compared to responders. The MADRS reduction and the changes in VEGF levels between V1 and V3 were significantly associated in responders only in the AD&amp;rTMS sample (p=0.03). The baseline VEGF level has been proven as a significant predictive factor of treatment response in the total sample (p=0.018).ConclusionsThe baseline VEGF level can be a predictive factor to be a non-responder to different treatments. Change of the VEGF level is associated with the improvement of depressive symptoms only due to rTMS.DisclosureThis study was supported by the FK 131315 grant of the National Research, Development and Innovation Office, Hungary. Authors declare no conflict of interest.

Peripheral vascular endothelial growth factor changes after transcranial magnetic stimulation in treatment-resistant depression.

To determine if vascular endothelial growth factor (VEGF) changes with transcranial magnetic stimulation (TMS) in treatment-resistant major depressive disorder (MDD). Serum from a naturalistic population of 15 patients with MDD was collected at baseline and after standard TMS treatment. VEGF concentration was determined via ELISA. Inventory of Depressive Symptomatology Self Report and Patient Health Questionnaire were used as a measure of depression symptom severity, clinical response and remission. Mann-Whitney U and Kendall's Tau Correlation were used for continuous variables. VEGF increased from pre- to post-TMS (+30.3%) in remitters whereas VEGF decreased in non-remitters (-9.87%) (P < 0.05). This same pattern was observed when comparing mean %change in VEGF between responders (+14.7%) and non-responders (-14.9%) (P = 0.054). Correlation was present between change in VEGF concentration (baseline to post) and change in Inventory of Depressive Symptomatology-Self Report at Tx30 (r = -0.371, P < 0.054), reflecting greater increases in VEGF linked to greater improvement in depressive symptoms following the standard 6-week course of TMS. Patients with a successful treatment with TMS had significantly greater increase in VEGF from baseline to after treatment compared to non-responders/non-remitters and a larger increase in VEGF was associated with greater improvement in depressive symptoms after TMS. This is the first report examining VEGF levels in depressed patients receiving TMS. This study provides correlative data supporting further investigation into VEGF's role as an important mediator in the processes underpinning TMS' antidepressant effects and as a potential biomarker of clinical outcomes.

Chronic stress followed by social isolation promotes depressive-like behaviour, alters microglial and astrocyte biology and reduces hippocampal neurogenesis in male mice

Unpredictable chronic mild stress (UCMS) is one of the most commonly used, robust and translatable models for studying the neurobiological basis of major depression. Although the model currently has multiple advantages, it does not entirely follow the trajectory of the disorder, whereby depressive symptomology can often present months after exposure to stress. Furthermore, patients with depression are more likely to withdraw in response to their stressful experience, or as a symptom of their depression, and, in turn, this withdrawal/isolation can further exacerbate the stressful experience and the depressive symptomology. Therefore, we investigated the effect(s) of 6 weeks of UCMS followed by another 6 weeks of social isolation (referred to as UCMSI), on behaviour, corticosterone stress responsivity, immune system functioning, and hippocampal neurogenesis, in young adult male mice. We found that UCMSI induced several behavioural changes resembling depression but did not induce peripheral inflammation. However, UCMSI animals showed increased microglial activation in the ventral dentate gyrus (DG) of the hippocampus and astrocyte activation in both the dorsal and ventral DG, with increased GFAP-positive cell immunoreactivity, GFAP-positive cell hypertrophy and process extension, and increased s100β-positive cell density. Moreover, UCMSI animals had significantly reduced neurogenesis in the DG and reduced levels of peripheral vascular endothelial growth factor (VEGF) – a trophic factor produced by astrocytes and that stimulates neurogenesis. Finally, UCMSI mice also had normal baseline corticosterone levels but a smaller increase in corticosterone following acute stress, that is, the Porsolt Swim Test. Our work gives clinically relevant insights into the role that microglial and astrocyte functioning, and hippocampal neurogenesis may play in the context of stress, social isolation and depression, offering a potentially new avenue for therapeutic target.

Peripheral blood mononuclear cells extracts VEGF protein levels and VEGF mRNA: Associations with inflammatory molecules in a healthy population.

BackgroundVascular endothelial growth factor (VEGF) is a signal protein, implicated in various physiological and pathophysiological processes together with other common inflammatory biomarkers. However, their associations have not yet been fully elucidated. In the present study, we investigated associations between VEGF and four specific VEGF mRNA isoforms with levels of 11 inflammation molecules, derived from peripheral blood mononuclear cells (PBMCs) extracts.MethodsHealthy participants from the STANISLAS Family Study (n = 285) were included. Levels of VEGF (four mRNA isoforms and protein levels) and inflammatory molecules (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, INF-γ, TNF-α, MCP-1, EGF) were measured in PBMCs extracts. Multiple regression analyses were performed, adjusted for age and gender.ResultsThe analyses revealed significant associations between VEGF protein levels and levels of IL-4 (β = 0.028, P = 0.013), MCP-1 (β = 0.015, P<0.0001) and EGF (β = 0.017, P<0.0001). Furthermore, mRNA isoform VEGF165 was associated with MCP-1 and IL-1α (P = 0.002 and P = 0.008, respectively); and mRNA isoform VEGF189 was associated with IL-4 and IL-6 (P = 0.019 and P = 0.034, respectively).ConclusionsTo our knowledge, the present study represents the first investigation that successfully demonstrates links between VEGF protein levels and inflammatory molecules levels derived from PBMCs extracts and identifies associations between specific VEGF mRNA isoforms and inflammatory molecules.ImpactThese findings provide novel insights that may assist in the development of new tissue and mRNA isoform specific measurements of VEGF levels, which may positively contribute to predicting the risk of common complex diseases and response of currently used anti-VEGF agents, and developing of novel targeted therapies for VEGF-related pathophysiology.

Portal Angiogenesis in Chronic Liver Disease Patients Correlates with Portal Pressure and Collateral Formation

Background/Aims: One hallmark of chronic liver disease in patients with portal hypertension is the formation of portal-systemic collaterals in which angiogenesis has a fundamental role. We studied patients with chronic liver disease undergoing liver transplantation to correlate levels of circulating angiogenic factors in portal and peripheral circulation with portal pressure and portal-systemic collaterals. Methods: Sixteen patients who underwent liver transplantation were enrolled. During transplant surgery, we determined portal venous pressure and portal-systemic collateral formation. We determined angiogenics mediator levels in systemic and portal plasma. Peripheral plasma from healthy donors was measured as controls. Results: Vascular endothelial growth factor (VEGF)-R1 and 2, Ang-1 and 2, Tie2, FGF- 1 and 2, CD163, PDGFR-β, PDGFsRα, PDGF-AB and BB, CD163, TGF-β VASH-1 levels were significantly different in the controls in comparison to cases. Significantly decreased portal venous levels of Ang-1, FGF-1, PDGF-AB/BB, and CC were observed in patients with higher portal pressure. Peripheral VEGF, Ang-1, pPDGF-AB, BB, and CC were significantly decreased in patients with more severe collateral formation. While peripheral VEGF-R1 was higher in patients with severe collateral formation. For portal circulation, VEGF, Ang-1, ­pPDGF-AB, BB, and CC were significantly decreased in patients with more severe collateral formation Conclusions: Angiogenesis factors correlated with portal pressure and collateral formation and different patterns of circulating angiogenesis mediators were found in peripheral and portal blood of patients with chronic liver disease. These results support the importance of angiogenic pathways in cirrhosis and portal hypertension and highlight areas for further study to identify clinically useful noninvasive markers of portal pressure and collateral formation.

Aerobic exercise promotes hippocampal neurogenesis through skeletal myofiber-derived vascular endothelial growth factor.

Aerobic exercise promotes hippocampal neurogenesis through skeletal myofiber-derived vascular endothelial growth factor.

Skeletal myofiber vascular endothelial growth factor is required for the exercise training-induced increase in dentate gyrus neuronal precursor cells.

Peripheral vascular endothelial growth factor (VEGF) is necessary for exercise to stimulate hippocampal neurogenesis. Here we report that skeletal myofiber VEGF directly or indirectly regulates exercise-signalled proliferation of neuronal precursor cells. Our results found skeletal myofiber VEGF to be necessary for maintaining blood flow through hippocampal regions independent of exercise training state. This study demonstrates that skeletal myofiber VEGF is required for the hippocampal VEGF response to acute exercise. These results help to establish the mechanisms by which exercise, through skeletal myofiber VEGF, affects the hippocampus. Exercise signals neurogenesis in the dentate gyrus of the hippocampus. This phenomenon requires vascular endothelial growth factor (VEGF) originating from outside the blood-brain barrier, but no cellular source has been identified. Thus, we hypothesized that VEGF produced by skeletal myofibers plays a role in regulating hippocampal neuronal precursor cell proliferation following exercise training. This was tested in adult conditional skeletal myofiber-specific VEGF gene-ablated mice (VEGFHSA-/- ) by providing VEGFHSA-/- and non-ablated (VEGFf/f ) littermates with running wheels for 14days. Following this training period, hippocampal cerebral blood flow (CBF) was measured by functional magnetic resonance imaging (fMRI), and neuronal precursor cells (BrdU+/Nestin+) were detected by immunofluorescence. The VEGFf/f trained group showed improvements in both speed and endurance capacity in acute treadmill running tests (P<0.05). The VEGFHSA-/- group did not. The number of proliferating neuronal precursor cells was increased with training in VEGFf/f (P<0.05) but not in VEGFHSA-/- mice. Endothelial cell (CD31+) number did not change in this region with exercise training or skeletal myofiber VEGF gene deletion. However, resting blood flow through the hippocampal region was lower in VEGFHSA-/- mice, both untrained and trained, than untrained VEGFf/f mice (P<0.05). An acute hypoxic challenge decreased CBF (P<0.05) in untrained VEGFf/f , untrained VEGFHSA-/- and trained VEGFHSA-/- mice, but not trained VEGFf/f mice. VEGFf/f , but not VEGFHSA-/- , mice were able to acutely run on a treadmill at an intensity sufficient to increase hippocampus VEGF levels. These data suggest that VEGF expressed by skeletal myofibers may directly or indirectly regulate both hippocampal blood flow and neurogenesis.

Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults

Animal models point towards a key role of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in mediating exercise-induced structural and functional changes in the hippocampus. Recently, also platelet derived growth factor-C (PDGF-C) has been shown to promote blood vessel growth and neuronal survival. Moreover, reductions of these neurotrophic and angiogenic factors in old age have been related to hippocampal atrophy, decreased vascularization and cognitive decline. In a 3-month aerobic exercise study, forty healthy older humans (60 to 77years) were pseudo-randomly assigned to either an aerobic exercise group (indoor treadmill, n=21) or to a control group (indoor progressive-muscle relaxation/stretching, n=19). As reported recently, we found evidence for fitness-related perfusion changes of the aged human hippocampus that were closely linked to changes in episodic memory function. Here, we test whether peripheral levels of BDNF, IGF-I, VEGF or PDGF-C are related to changes in hippocampal blood flow, volume and memory performance. Growth factor levels were not significantly affected by exercise, and their changes were not related to changes in fitness or perfusion. However, changes in IGF-I levels were positively correlated with hippocampal volume changes (derived by manual volumetry and voxel-based morphometry) and late verbal recall performance, a relationship that seemed to be independent of fitness, perfusion or their changes over time. These preliminary findings link IGF-I levels to hippocampal volume changes and putatively hippocampus-dependent memory changes that seem to occur over time independently of exercise. We discuss methodological shortcomings of our study and potential differences in the temporal dynamics of how IGF-1, VEGF and BDNF may be affected by exercise and to what extent these differences may have led to the negative findings reported here.

Association of serum VEGF levels with prefrontal cortex volume in schizophrenia.

A large body of evidence indicates alterations in brain regional cellular energy metabolism and blood flow in schizophrenia. Among the different molecules regulating blood flow, vascular endothelial growth factor (VEGF) is generally accepted as the major factor involved in the process of angiogenesis. In the present study, we examined whether peripheral VEGF levels correlate with changes in the prefrontal cortex (PFC) volume in patients with schizophrenia and in healthy controls. Whole-blood samples were obtained from 96 people with schizophrenia or schizoaffective disorder and 83 healthy controls. Serum VEGF protein levels were analyzed by enzyme-linked immunosorbent assay, whereas quantitative PCR was performed to measure interleukin-6 (IL-6, a pro-inflammatory marker implicated in schizophrenia) mRNA levels in the blood samples. Structural magnetic resonance imaging scans were obtained using a 3T Achieva scanner on a subset of 59 people with schizophrenia or schizoaffective disorder and 65 healthy controls, and prefrontal volumes were obtained using FreeSurfer software. As compared with healthy controls, individuals with schizophrenia had a significant increase in log-transformed mean serum VEGF levels (t(177)=2.9, P=0.005). A significant inverse correlation (r=-0.40, P=0.002) between serum VEGF and total frontal pole volume was found in patients with schizophrenia/schizoaffective disorder. Moreover, we observed a significant positive association (r=0.24, P=0.03) between serum VEGF and IL-6 mRNA levels in patients with schizophrenia. These findings suggest an association between serum VEGF and inflammation, and that serum VEGF levels are related to structural abnormalities in the PFC of people with schizophrenia.

0295: Increased intracardiac VEGF and VWF levels revealed low grade inflammatory process and progressive endothelial damage in patients with atrial fibrillation

Endothelial dysfunction seems to play a pivotal role in atrial fibrillation (AF). The purpose of this study was to investigate the relationship between AF and vascular endothelial growth factor (VEGF) and to investigate the effect of different clinical forms of AF on plasma concentration of Von Willebrand Factor (vWF) at different levels of circulatory tree, both intracardiac and extracardiac. Peripheral (Pf), left atrial (LA), and coronary sinus (CS) blood samples were obtained during cardiac catheterization from 52 patients with paroxysmal AF (PAF), 36 with persistent AF (PsAF), and 17 control subjects (Ct) with Wolff-Parkinson-White syndrome. Plasma levels of VEGF and vWF were measured at the three sampled sites. Peripheral VEGF levels were higher in both PAF and PsAF patients than in controls (P≤0.03). Left atrial VEGF levels were higher in paroxysmal AF (P = 0.05), but not in persistent AF (P = 0.32), compared with controls. Coronary sinus and pulmonary vein VEGF levels did not differ significantly among groups. (Fig 1). Compared with Ct, patients with PAF had higher LA plasma levels of vWF (P=0.004), but similar Pf and CS levels (both P>0.30). In contrast, patients with PsAF had higher plasma concentrations of vWF in Pf (P=0.04), LA (P<0.001), and CS (P=0.04) samples compared with Ct. Left atrial plasma concentrations of vWF in patients with PsAF were also higher than in the PAF group (P=0.04). (Fig 1, next page). This study suggests that inflammatory process in AF is of low grade. The heart itself is the most likely source of high left atrial VEGF; however, this disorder appears to be a transient event in AF history. AF patients presented significantly higher plasma concentrations of vWF. This study suggests an association between the clinical evolution of AF and the progression of endothelial dysfunction. Further studies will have to establish the exact mechanisms that link endothelial dysfunction and stroke in the context of AF. Abstract 0295 – Figure: VEGF and Vwf plasma levels in the 3 study groups

The role of skeletal myofiber VEGF in the cerebral neurogenic response to exercise (706.21)

Exercise induces cerebral neurogenesis. This phenomenon has been suggested to require peripheral vascular endothelial growth factor (VEGF). We hypothesized that skeletal myofiber VEGF may regulate blood flow and neurogenesis in the hippocampus. This was tested in adult skeletal myofiber specific VEGF gene ablated mice (skmVEGF‐/‐) provided running wheels for 14 days. We measured exercise capacity, neurogenesis (BrDU+/NeuN+ cells) and post‐training cerebral blood flow (CBF) detected by fMRI. Voluntary distances ran each day did not differ between groups. There was a trend for higher BrDU+/NeuN+ cells/0.1 mm2 in WT mice (WT, 4.8+2.0, skmVEGF‐/‐ 1.8+0.6; p=0.08). CBF in mice breathing 21% or 10% O2 did not differ between groups. Endurance was increased in WT compared to skmVEGF‐/‐ mice post‐training (Pre‐training; WT 80+15 min., skmVEGF‐/‐, 27+5 min., Post‐training; WT 107+21 min., skmVEGF‐/‐, 42+8 min., p&lt;0.05). Speed improved in WT mice with training (Pre‐training; WT 61+2 cm/s, skmVEGF‐/‐, 51+3 cm/s, Post‐training; WT 69+3 cm/s, skmVEGF‐/‐, 61+4 cm/s, p&lt;0.05). These data suggest that myofiber VEGF, independent of CBF, may regulate exercise‐induced neurogenesis.Grant Funding Source: American Heart Association

0136: Increased intracardiac VEGF and VWF levels revealed low grade inflammatory process and progressive endothelial damage in patients with AF

Endothelial dysfunction seems to play a pivotal role in atrial fibrillation (AF). The purpose of this study was to investigate the relationship between AF and vascular endothelial growth factor (VEGF) and to investigate the effect of different clinical forms of AF on plasma concentration of Von Willebrand Factor (vWF) at different levels of circulatory tree, both intracardiac and extracardiac. Peripheral (Pf), left atrial (LA), and coronary sinus (CS) blood samples were obtained during cardiac catheterization from 52 patients with paroxysmal AF (PAF), 36 with persistent AF (PsAF), and 17 control subjects (Ct) with Wolff-Parkinson-White syndrome. Plasma levels of VEGF and vWF were measured at the three sampled sites. Peripheral VEGF levels were higher in both PAF and PsAF patients than in controls (P≤0.03). Left atrial VEGF levels were higher in paroxysmal AF (P=0.05), but not in persistent AF (P=0.32), compared with controls. Coronary sinus and pulmonary vein VEGF levels did not differ significantly among groups. Compared with Ct, patients with PAF had higher LA plasma levels of vWF (P=0.004), but similar Pf and CS levels (both P>0.30). In contrast, patients with PsAF had higher plasma concentrations of vWF in Pf (P=0.04), LA (P<0.001), and CS (P=0.04) samples compared with Ct. Left atrial plasma concentrations of vWF in patients with PsAF were also higher than in the PAF group (P=0.04). This study suggests that inflammatory process in AF is of low grade. The heart itself is the most likely source of high left atrial VEGF; however, this disorder appears to be a transient event in AF history. AF patients presented significantly higher plasma concentrations of vWF. This study suggests an association between the clinical evolution of AF and the progression of endothelial dysfunction. Further studies will have to establish the exact mechanisms that link endothelial dysfunction and stroke in the context of AF. Abstract 0136 – Figure: vWF and VEGF plasma levels in the 3 study groups

Vascular endothelial growth factor gene (VEGFA) polymorphisms may serve as prognostic factors for recurrent depressive disorder development

Recurrent depressive disorder (rDD) is a multifactorial disease. Vascular endothelial growth factor (VEGF) is one of the factors that have been suggested to play a role in the etiology and/or development of this disease. Limited information related to the role of VEGFA gene polymorphism in depressive disorder is available. The aim of the study was to analyze the association between VEGFA gene polymorphisms (+405G/C; rs2010963, +936C/T; rs 3025039), VEGFA gene expression, and its serum protein levels in rDD in the Caucasian population. In the current study, 268 patients and 200 healthy controls of the Caucasian origin were involved. Genotyping and gene expression were performed using polymerase chain reaction (PCR)-based methods. Enzyme-linked immunosorbent assay (ELISA) was used for detection of circulating serum VEGF levels. The distribution of VEGFA polymorphism +405G/C differed significantly between rDD patients and healthy subjects. The results of this study indicated that the C allele and CC genotype of VEGFA are risk factors for rDD. Haplotypes CC and TG are the important factors for depression development. Further, VEGFA mRNA expression and VEGF levels were higher in rDD patients than in controls. The VEGFA gene polymorphism may serve as a prognostic factor for rDD development. Our study showed higher levels of both VEGFA mRNA in the peripheral blood cells and serum VEGF in patients diagnosed with rDD than in healthy controls. The obtained results suggest VEGF and the gene encoding the molecule play a role in the etiology of the disease and should be further investigated.

Peripheral vascular endothelial growth factor level is associated with antidepressant treatment response: Results of a preliminary study

BackgroundRecent investigations have revealed multiple actions of vascular endothelial growth factor (VEGF) in the nervous system. The role of VEGF in the molecular background of mood disorders has also been proposed. In this study we were interested in investigating a possible association between VEGF levels and treatment response in patients with a current episode of major depression (MDE). Methods34 patients with MDE were enrolled in our study. Depressive symptoms were monitored by the Montgomery–Åsberg Depression Rating Scale at baseline (V1) and after a 4-week treatment period (V2). Patients with less than a 50% improvement in MADRS total scores during this period were regarded as non-responders. ResultsPlasma VEGF levels did not change during the treatment period in either the total sample or in the responder and non-responder subsamples. There was a strong trend for higher baseline VEGF levels in the non-responder group than in the responder group (p=0.055) and this difference—as a weak trend—was still detectable at the end of the treatment period (p=0.097). Regression analysis revealed that the baseline VEGF level was a significant predictor for the endpoint MADRS score (p=0.02). LimitationsSample size was relatively small; sample consists of both patients with MDD and bipolar disorder. ConclusionsOur preliminary results raise the possibility that baseline levels of peripheral VEGF may predict treatment response in patients with mood disorders. Considering the limitations of our study, further investigations should resolve whether VEGF is a useful biomarker for treatment response in depression in clinical practice.

Increased intracardiac vascular endothelial growth factor levels in patients with paroxysmal, but not persistent atrial fibrillation

Although inflammation appears to play a pivotal role in the pathophysiology of atrial fibrillation (AF), the source of inflammation is unknown. We hypothesized that multilevel measurement of several inflammatory proteins in AF patients would help assess the extent and the source of inflammation. Thirty-nine patients with paroxysmal AF, 33 with persistent AF, and 9 control patients with Wolff-Parkinson-White syndrome were enrolled. Peripheral, left atrial, coronary sinus, and pulmonary vein blood samples were obtained during catheterization. Serum levels of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), soluble intercellular adhesion molecule 1 (sICAM-1), and transforming growth factor-β1 (TGF-β1) were measured at the four sampled sites. Interleukin-8, sICAM-1, and TGF-β1 levels did not differ among groups at any of the sampled sites. Peripheral VEGF levels were higher in both paroxysmal and persistent AF patients than in controls (P ≤ 0.03). Left atrial VEGF levels were higher in paroxysmal AF (P = 0.05), but not in persistent AF (P = 0.32), compared with controls. Coronary sinus and pulmonary vein VEGF levels did not differ significantly among groups. Low levels of several inflammatory markers in both paroxysmal and persistent AF patients suggest that the inflammatory process is of low grade, if present. In the context of normal pulmonary vein VEGF levels, the heart itself is the most likely source of high left atrial VEGF levels in paroxysmal AF patients; however, this disorder appears to be a transient event in the natural history of AF.

Granulocyte Colony-Stimulating Factor Reduces Hyperoxia-Induced Alveolarization Inhibition by Increasing Angiogenic Factors

Background: Granulocyte colony-stimulating factor (G-CSF) is known to mobilize endothelial progenitor cells (EPCs) from bone marrow. EPCs reportedly promote neovascularization and participate in the repair of lung structure in adult animals. Objective: We tested the hypothesis that G-CSF contributes to alveolar growth by increasing the production of angiogenic growth factor in the lungs of hyperoxia-exposed neonatal mice. Methods: Neonatal mice were exposed to hyperoxia (80%) or room air (RA) for 7 days and treated with G-CSF (50 µg/kg/day) or vehicle for 5 days. Blood was subjected to flow cytometry to gate for CD45^dim/–/Sca-1⁺/CD133⁺/vascular endothelial growth factor (VEGF) receptor-2 (VEGFR2) to define the EPC population at day 7. Results: The percentage of EPCs in the peripheral blood and VEGF and VEGFR2 levels in the lungs of neonatal mice exposed to hyperoxia were significantly reduced compared to those of mice kept in RA. G-CSF significantly increased EPCs in the peripheral blood, and VEGF and VEGFR2 levels in the lungs of both mice exposed to hyperoxia and mice kept in RA. G-CSF restored alveolarization inhibited by hyperoxia without altering normal alveolarization under RA. Conclusion: G-CSF restored alveolarization inhibited by hyperoxia in the developing lungs and this alveolarization-enhancing effect of G-CSF is associated with mobilization of EPCs and upregulation of VEGF signaling.

Serum albumin and vascular endothelial growth factor in epithelial ovarian cancer: looking at adnexal tumor drainage

This study aims to analyze serum albumin levels (SAL) in relation to concentrations of vascular endothelial growth factor (VEGF) from peripheral plasma, infundibular plasma, peritoneal fluids and the peritoneal burden of VEGF of patients with epithelial ovarian cancer. Exploratory analyses of SAL in 39 patients and its relation to mean concentrations of VEGF from the origins are described above. Statistical analyses comprised Student's t test, Mann-Whitney test and Pearson's and Spearman's correlation coefficient. Both infundibular concentrations of VEGF and the peritoneal burden of VEGF showed significant differences between SAL dichotomized at 3 g/dl. Concentrations of VEGF in peritoneal fluids were not significant in relation to SAL. Peripheral plasma VEGF levels did not show any linear correlation with SAL. Indeed, SAL showed a significant negative linear correlation (p < 0.001) to infundibular plasma as well as the peritoneal burden of VEGF (p = 0.004). Infundibular mean concentrations of VEGF may contribute to reduce SAL in advanced staging rather than the peripheral plasma concentrations of this glycoprotein. The peritoneal burden of VEGF may also aid in decreasing levels of serum albumin.

Peripheral blood dendritic cells and vascular endothelial growth factor in oral squamous cell carcinoma: correlation analysis and in vitro study

Vascular endothelial growth factor (VEGF) may cause functional deficiency in dendritic cells (DCs) in vitro. The roles of peripheral blood dendritic cells (PBDCs) and VEGF in patients with oral squamous cell carcinoma (OSCC) are not well understood. The authors analysed the correlation between VEGF and PBDC in 81 OSCC patients. They assessed the effect of VEGF on DC function in vitro. VEGF levels were significantly increased in OSCC patients compared with control subjects (P < 0.05), but PBDC levels were significantly lower (P < 0.05). VEGF expression in TNM I-II (67%) and T1-T2 (74%) was significantly lower, compared with TNM III-IV (88%, P < 0.05) and T3-T4 (89%, P < 0.05). Increased VEGF expression in primary tumours was significantly correlated with elevated serum VEGF levels, but reduced PBDC levels. In vitro cultured DC exposed to VEGF showed significantly decreased expression of functional proteins, enhanced endocytosis activity, and elicited weaker proliferation of T cells, compared with that of free VEGF (P < 0.01). These findings suggest that decreased PBDC and elevated VEGF occur in OSCC patients. Higher VEGF levels may affect precursor cells, resulting in decreased numbers of functional DC.