Sildenafil ameliorates Alzheimer disease via the modulation of vascular endothelial growth factor and vascular cell adhesion molecule-1 in rats

2020 ◽  
pp. 096032712096077
Author(s):  
MA Ibrahim ◽  
MASA Haleem ◽  
SA AbdelWahab ◽  
AM Abdel-Aziz
Keyword(s):  
Oxidative Stress ◽  
Cell Adhesion Molecule ◽  
Vascular Endothelial ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Stress Markers ◽  
Tnf Α ◽  
Cell Adhesion Molecule 1 ◽  
Endothelial Growth Factor ◽  
And Oxidative Stress

Alzheimer disease (AD) is a chronic neurodegenerative disease with multi-pathways pathogenesis. Sildenafil is a selective phosphodiesterase-5 inhibitor with a potential benefit in the treatment of AD. This study investigated the possible mechanisms underlying the effect of sildenafil in AD with emphasis on vascular endothelial growth factor (VEGF), and vascular cell adhesion molecule-1 (VCAM-1). Twenty-four adult male rats were classified into four groups; control group: received vehicles, sildenafil–control: received sildenafil (15 mg/kg/day, p.o.), AD group received Aluminum (25 mg/kg/day, p.o.), AD-treated group: received sildenafil (15 mg/kg/day, p.o.) for 6 weeks. AD was assessed by memory performance test and confirmed by histopathological examination and immunostaining of, neurogenesis marker nestin and α-synuclein. The levels of VEGF-A, VCAM-1, oxidative stress markers and TNF-α in brain tissue were evaluated. AD rats showed histopathological evidences of AD; along with increased latency time in the memory test. There was a decrease in VEGF-A, and an increase in VCAM-1, TNF-α, and oxidative stress markers. Immunohistochemical study showed a significant increase in α-synuclein and a significant decrease in nestin expressions in brain tissues. Sildenafil administration ameliorated the histopathological changes and decreased latency time. Such effect was associated with a decrease in VCAM-1, TNF-α and oxidative stress as well as an increase in VEGF-A. Sildenafil caused a significant increase in nestin and a decrease in α-synuclein immunostaining. These findings suggested a protective effect of sildenafil via modulation of VEGF-A, and VCAM-1.

scholarly journals A Novel STAT3-Mediated GATA6 Pathway Contributes to tert-Butylhydroquinone- (tBHQ-) Protected TNFα-Activated Vascular Cell Adhesion Molecule 1 (VCAM-1) in Vascular Endothelium

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Li Zhou ◽  
Hua Ning ◽  
Haibin Wei ◽  
Tiantian Xu ◽  
Xindi Zhao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vascular Endothelium ◽  
Cell Adhesion Molecule ◽  
Vascular Endothelial Cells ◽  
Protective Role ◽  
Vascular Endothelial ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Cell Adhesion Molecule 1

The activation of vascular cell adhesion molecule 1 (VCAM-1) in vascular endothelial cells has been well considered implicating in the initiation and processing of atherosclerosis. Oxidative stress is mechanistically involved in proatherosclerotic cytokine-induced VCAM-1 activation. tert-Butylhydroquinone (tBHQ), a synthetic phenolic antioxidant used for preventing lipid peroxidation of food, possesses strongly antioxidant capacity against oxidative stress-induced dysfunction in various pathological process. Here, we investigated the protective role of tBHQ on tumor necrosis factor alpha- (TNFα-) induced VCAM-1 activation in both aortic endothelium of mice and cultured human vascular endothelial cells and uncovered its potential mechanisms. Our data showed that tBHQ treatment significantly reversed TNFα-induced activation of VCAM-1 at both transcriptional and protein levels. The mechanistic study revealed that inhibiting neither nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nor autophagy blocked the beneficial role of tBHQ. Alternatively, tBHQ intervention markedly alleviated TNFα-increased GATA-binding protein 6 (GATA6) mRNA and protein expressions and its translocation into nucleus. Further investigation indicated that tBHQ-inhibited signal transducer and activator of transcription 3 (STAT3) but not mitogen-activated protein kinase (MAPK) pathway contributed to its protective role against VCAM-1 activation via regulating GATA6. Collectively, our data demonstrated that tBHQ prevented TNFα-activated VCAM-1 via a novel STAT3/GATA6-involved pathway. tBHQ could be a potential candidate for the prevention of proatherosclerotic cytokine-caused inflammatory response and further dysfunctions in vascular endothelium.

Association of Preoperative Plasma Levels of Vascular Endothelial Growth Factor and Soluble Vascular Cell Adhesion Molecule-1 With Lymph Node Status and Biochemical Progression After Radical Prostatectomy

2004 ◽  
Vol 22 (9) ◽  
pp. 1655-1663 ◽  
Author(s):  
Shahrokh F. Shariat ◽  
Veronica A. Anwuri ◽  
Dolores J. Lamb ◽  
Nina V. Shah ◽  
Thomas M. Wheeler ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Cell Adhesion Molecule ◽  
Vascular Endothelial ◽  
Healthy Controls ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Localized Disease ◽  
Biochemical Progression ◽  
Cell Adhesion Molecule 1 ◽  
Endothelial Growth Factor

Purpose Angiogenesis is a critical process for cancer progression. We tested whether elevated circulating levels of the angiogenesis-related markers vascular endothelial growth factor (VEGF) and/or soluble vascular cell adhesion molecule-1 (sVCAM-1) are associated with prostate cancer diagnosis, stage, progression, and metastasis. Patients and Methods Plasma levels of VEGF and sVCAM-1 were measured on frozen, archival plasma obtained preoperatively from 215 consecutive patients who underwent radical prostatectomy for clinically localized disease, nine men with untreated prostate cancer metastatic to bones, and 40 healthy men without cancer. Results Plasma levels of both VEGF and sVCAM-1 were highest in patients with bone metastases (P < .001). VEGF levels were higher in patients with clinically localized disease than in healthy controls (P < .001). VEGF levels were elevated in patients with biopsy and final Gleason sum ≥ 7 (P = .036 and P = .020, respectively) and extraprostatic extension (P = .047). Higher preoperative VEGF was independently associated with metastases to lymph nodes (P < .001). Both VEGF and sVCAM-1 were independently associated with biochemical progression after adjustment for the effects of standard preoperative features (P = .014 and P = .039, respectively). VEGF remained independently associated with biochemical progression after adjustment for standard postoperative features (P = .019). Conclusion Plasma levels of VEGF increased incrementally from healthy controls to patients with clinically localized disease to patients with lymph node and skeletal metastases. Higher preoperative VEGF was independently associated with metastases to lymph nodes and biochemical progression after surgery in both pre- and postoperative models. Plasma sVCAM-1 was elevated in men with bone metastases and was associated with biochemical progression in a preoperative model.

scholarly journals Recombinant vascular endothelial growth factor 121 decreases vascular cell adhesion molecule-1 in murine pre-eclampsia model placenta

2016 ◽  
Vol 35 (3) ◽  
pp. 192
Author(s):  
Sri Sulistyowati ◽  
John Arianto Sondakh ◽  
Eric Edwin Yuliantara ◽  
Supriyadi Hari Respati ◽  
Soetrisno Soetrisno
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cell Adhesion Molecule ◽  
Angiogenic Factor ◽  
Vascular Endothelial ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Pregnant Mice ◽  
Cell Adhesion Molecule 1 ◽  
Endothelial Growth Factor

Background<br />Preeclampsia is one of the major contributors to maternal and fetal morbidity and mortality. Imbalance of soluble Fms-like tyrosine kinase (sFlt-1) as anti-angiogenic factor and vascular endothelial growth factor (VEGF) as pro-angiogenic factor plays a role in the pathogenesis of preeclampsia. Endothelial dysfunction in preeclampsia causes vascular cell adhesion molecule-1 (VCAM-1) to be expressed on its surface. This study aims to evaluate the effect of recombinant VEGF-121 on VCAM-1 expression in the placenta of a murine preeclampsia model. <br /><br />Methods <br />An experimental analytical study conducted from February until March 2016 in the Biomedical Laboratory, Faculty of Veterinary Medicine, Airlangga University. The study sample consisted of 30 pregnant mice, divided into three groups, i.e. 10 normal pregnant mice, 10 mice with preeclampsia model and 10 mice with preeclampsia model and recombinant VEGF-121 therapy. All animals were subjected to immunohistochemical examination of VCAM-1 expression in their placentas. The results were assessed semiquantitatively according to a modified Remmele method. Data analysis was done using one-way ANOVA and Tukey’s multiple comparisons method. <br /><br />Results<br />Mean VCAM-1 expression in normal (0.97 ± 0.54%) murine placentas, compared with placentas (2.94 ± 0.96%) of murine preeclampsia models (p=0.000), while mean VCAM-1 expression in placentas of murine preeclampsia models with VEGF intervention was 2.14 ± 0.68% (p=0.030).<br /><br />Conclusion <br />Recombinant VEGF-121 can reduce VCAM-1 expression in placentas of murine preeclampsia models. The present study has shown the potential benefits of VEGF therapy, justifying serious consideration of this therapeutic approach for use in women with preeclampsia.

scholarly journals Conjugated linoleic acid increased C-reactive protein in human subjects

2005 ◽  
Vol 94 (5) ◽  
pp. 791-795 ◽  
Author(s):  
Annika Smedman ◽  
Samar Basu ◽  
Stefan Jovinge ◽  
Gunilla Nordin Fredrikson ◽  
Bengt Vessby
Keyword(s):  
Cell Adhesion ◽  
Linoleic Acid ◽  
Cell Adhesion Molecule ◽  
Human Subjects ◽  
Vascular Cell Adhesion ◽  
C Reactive Protein ◽  
Vascular Cell ◽  
Reactive Protein ◽  
Tnf Α ◽  
Cell Adhesion Molecule 1

We previously showed that conjugated linoleic acid (CLA) increases 15-keto-dihydro-prostaglandin F2α, a marker for cyclooxygenase-mediated lipid peroxidation and thus an indicator of cyclooxygenase-mediated inflammation. The aim of the present study was to investigate the effects of CLA on other indicators of inflammation in human subjects, including C-reactive protein, TNF-α, TNF-α receptors 1 and 2, and vascular cell adhesion molecule-1. In a double-blind, placebo-controlled study, fifty-three human subjects were supplemented with a mixture (4·2g/d) of the isomers cis-9,trans-11 CLA and trans-10,cis-12 CLA or control oil for 3 months. CLA supplementation increased levels of C-reactive protein (P=0·003) compared with the control group. However, no changes in TNF-α, TNF-α receptors 1 and 2, and vascular cell adhesion molecule-1 were detected.

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