scholarly journals PTEN inhibitor improves vascular remodeling and cardiac function after myocardial infarction through PI3k/Akt/VEGF signaling pathway

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Qiuting Feng ◽  
Xing Li ◽  
Xian Qin ◽  
Cheng Yu ◽  
Yan Jin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Signaling Pathway ◽  
Cardiomyocyte Apoptosis ◽  
Therapeutic Drug ◽  
Vascular Endothelial ◽  
Vegf Signaling ◽  
Endothelial Growth Factor ◽  
To Receive ◽  
Vegf Signaling Pathway

Abstract Background Myocardial infarction (MI) is the leading cause of death from cardiovascular disease (CVD). Currently, the efficacy for MI treatment remains unsatisfactory. Therefore, it is urgent to develop a novel therapeutic strategy. Methods Left anterior descending arteries (LAD) of mice were ligated to induce MI. Another set of mice were intravenously injected with PTEN inhibitor BPV (1 mg/kg) 1 h after LAD ligation and continued to receive BPV injection daily for the following 6 days. Mice were performed echocardiography 14 days after surgery. Results Mice in MI group displayed an increased expression of PTEN with impaired cardiac function, enhanced cardiomyocyte apoptosis and decreased angiogenesis. BPV treatment significantly improved cardiac function, with reduced cardiomyocyte apoptosis, promoted angiogenesis, and activated PI3K/Akt/vascular endothelial growth factor (VEGF) signaling pathway. Conclusion PTEN inhibitor BPV could effectively prevent myocardial infarction in mice, highlighting its potential as a candidate therapeutic drug.

scholarly journals Correlation between vascular endothelial growth factor pathway and immune microenvironment in head and neck squamous cell carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chao Zhu ◽  
Liqun Gu ◽  
Zelong Liu ◽  
Jiang Li ◽  
Mianfeng Yao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Immune Cell ◽  
Vascular Endothelial ◽  
Related Gene ◽  
Immune Microenvironment ◽  
Vegf Signaling ◽  
Immune Related Gene ◽  
Tumor Immune Microenvironment ◽  
Endothelial Growth Factor ◽  
Vegf Signaling Pathway

Abstract Background Immunotherapy is a crucial therapeutic approach in oncology. However, most patients with head and neck squamous cell carcinoma (HNSCC) do not derive benefit from immunotherapy. Vascular endothelial growth factor (VEGF)/VEGF Receptor 2 (VEGFR2) signaling pathway is one of the most important pathways regulating angiogenesis in tumor. The combination of immunotherapy and anti-angiogenic therapy is considered to improve efficacy of immunotherapy. The correlation between VEGF signaling pathway and tumor immune microenvironment in HNSCC patients is unclear. Methods We utilized RNA sequencing and clinical data of HNSCC patients from the TCGA database to study the correlation between VEGF signaling pathway and tumor immune microenvironment, on aspect of immune cell infiltration, immune-related gene expression profiling and immune-related biological pathways. Results We observed that VEGF signaling pathway is positively correlated with immune cell infiltration, immune-related gene expression profiles, and the prognosis of HNSCC patients. The functional enrichment analysis of differentially expressed genes between different VEGF score subtypes detected multiple immune-related biological processes. Conclusion Our findings suggested that combining anti-VEGF signaling pathway agents with immunotherapy, such as immune checkpoint inhibitors (ICI) therapy, may exhibit encouraging benefits in HNSCC.

Rational Design of Anti-Angiogenic Peptides to Inhibit VEGF/VEGFR2 Interactions for Cancer Therapeutics

2021 ◽  
Vol 21 ◽  
Author(s):  
Samaneh Ghasemali ◽  
Safar Farajnia ◽  
Abolfazl Barzegar ◽  
Mohammad Rahmati-yamchi ◽  
Babak Negahdari ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Rational Design ◽  
Mutation Screening ◽  
Dynamics Simulation ◽  
Vascular Endothelial ◽  
Vegf Signaling ◽  
Endothelial Growth Factor ◽  
Vegf Signaling Pathway

Background: Angiogenesis is a critical physiological process that plays a key role in tumor progression, metastatic dissemination, and invasion. In the last two decades, the vascular endothelial growth factor (VEGF) signaling pathway has been the area of extensive researches. VEGF executes its special effects by binding to vascular endothelial growth factor receptors (VEGFRs), particularly VEGFR-2. Objective: The inhibition of VEGF/VEGFR2 interaction is known as an effective cancer therapy strategy. The current study pointed to design and model an anti-VEGF peptide based on VEGFR2 binding regions. Method: The large-scale peptide mutation screening was used to achieve a potent peptide with high binding affinity to VEGF for possible application in inhibition of VEGF/VEGFR2 interaction. The AntiCP and Peptide Ranker servers were used to generate the possible peptides library with anticancer activities and prediction of peptides bioactivity. Then, the interaction of VEGF and all library peptides were analyzed using Hex 8.0.0 and ClusPro tools. A number of six peptides with favorable docking scores were achieved. All of the best docking scores of peptides in complexes with VEGF were evaluated to confirm their stability, using molecular dynamics simulation (MD) with the help of the GROMACS software package. Results: As a result, two antiangiogenic peptides with 13 residues of PepA (NGIDFNRDFFLGL) and PepC (NGIDFNRDKFLFL) were achieved and introduced to inhibit VEGF/VEGFR2 interactions. Conclusions: In summary, this study provided new insights into peptide-based therapeutics development for targeting VEGF signaling pathway in tumor cells. PepA and PepC are recommended as potentially promising anticancer agents for further experimental evaluations.

scholarly journals Buyang Huanwu Decoction Exerts Cardioprotective Effects through Targeting Angiogenesis via Caveolin-1/VEGF Signaling Pathway in Mice with Acute Myocardial Infarction

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Jia-Zhen Zhu ◽  
Xiao-Yi Bao ◽  
Qun Zheng ◽  
Qiang Tong ◽  
Peng-Chong Zhu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Treated Group ◽  
Border Zone ◽  
Vascular Endothelial ◽  
Buyang Huanwu Decoction ◽  
Caveolin 1 ◽  
Vegf Signaling ◽  
Cardioprotective Effects ◽  
Endothelial Growth Factor ◽  
Vegf Signaling Pathway

Background. Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. The idea of therapeutic angiogenesis in ischemic myocardium is a promising strategy for MI patients. Buyang Huanwu decoction (BHD), a famous Chinese herbal prescription, exerted antioxidant, antiapoptotic, and anti-inflammatory effects, which contribute to cardio-/cerebral protection. Here, we aim to investigate the effects of BHD on angiogenesis through the caveolin-1 (Cav-1)/vascular endothelial growth factor (VEGF) pathway in MI model of mice. Materials and Methods. C57BL/6 mice were randomly divided into 3 groups by the table of random number: (1) sham-operated group (sham, n=15), (2) AMI group (AMI+sham, n=20), and (3) BHD-treated group (AMI+BHD, n=20). 2,3,5-Triphenyltetrazolium chloride solution stain was used to determine myocardial infarct size. Myocardial histopathology was tested using Masson staining and hematoxylin-eosin staining. CD31 immunofluorescence staining was used to analyze the angiogenesis in the infarction border zone. Western blot analysis, immunofluorescence staining, and/or real-time quantitative reverse transcription polymerase chain reaction was applied to test the expression of Cav-1, VEGF, vascular endothelial growth factor receptor 2 (VEGFR2), and/or phosphorylated extracellular signal-regulated kinase (p-ERK). All statistical analyses were performed using the SPSS 20.0 software and GraphPad Prism 6.05. Values of P<0.05 were considered as statistically significant. Results and Conclusion. Compared with the AMI group, the BHD-treated group showed a significant improvement in the heart weight/body weight ratio, echocardiography images, cardiac function, infarct size, Mason staining of the collagen deposition area, and density of microvessel in the infarction border zone (P<0.05). Compared with the AMI group, BHD promoted the expression of Cav-1, VEGF, VEGFR2, and p-ERK in the infarction border zone after AMI. BHD could exert cardioprotective effects on the mouse model with AMI through targeting angiogenesis via Cav-1/VEGF signaling pathway.

scholarly journals Hypertension related to the antitumor treatment with angiogenesis inhibitors: an iatrogenic hypertension

2018 ◽  
Vol 24 (4) ◽  
pp. 384-395
Author(s):  
Zh. D. Kobalava ◽  
E. K. Shavarova
Keyword(s):  
Blood Pressure ◽  
Angiogenesis Inhibitors ◽  
Cardiovascular Complications ◽  
Vascular Endothelial ◽  
Vegf Inhibitors ◽  
Vegf Signaling ◽  
New Class ◽  
Potent Vasodilator ◽  
Endothelial Growth Factor ◽  
Vegf Signaling Pathway

One of the key regulators of vascular tone is the vascular endothelial growth factor (VEGF), which can enhance the production of nitric oxide, a potent vasodilator, and reduce vascular resistance by generating new vessels. Both mechanisms contribute to blood pressure decrease. The implementation of a new class of antitumor therapy — inhibitors of VEGF signaling pathway — results in the growth of cardiovascular complications such as arterial hypertension (HTN). The paper analyzes the causes of HTN development, approaches to the timely diagnosis of HTN and the correct assessment of cardiovascular risk before administration of VEGF inhibitors and during the treatment. We also review the features of the approaches of elevated blood pressure management in patients receiving targeted therapy.

scholarly journals Cell Transplantation for the Treatment of Acute Myocardial Infarction Using Vascular Endothelial Growth Factor–Expressing Skeletal Myoblasts

Circulation ◽  
2001 ◽  
Vol 104 (suppl_1) ◽  
Author(s):  
Ken Suzuki ◽  
Bari Murtuza ◽  
Ryszard T. Smolenski ◽  
Ivan A. Sammut ◽  
Noriko Suzuki ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cardiac Function ◽  
Vascular Endothelial ◽  
Skeletal Myoblast ◽  
Skeletal Myoblasts ◽  
Endothelial Growth Factor ◽  
Host Myocardium

Background Vascular endothelial growth factor (VEGF) is a promising reagent for inducing myocardial angiogenesis. Skeletal myoblast transplantation has been shown to improve cardiac function in chronic heart failure models by regenerating muscle. We hypothesized that transplantation of VEGF-expressing myoblasts could effectively treat acute myocardial infarction by providing VEGF-induced cardioprotection through vasodilatation in the early phase, followed by angiogenesis effects in salvaging ischemic host myocardium combined with the functional benefits of newly formed, skeletal myoblast-derived muscle in the later phase. Methods and Results Primary rat skeletal myoblasts were transfected with the human VEGF 165 gene using hemagglutinating virus of Japan-liposome with >95% transfection efficiency. Four million of these myoblasts (VEGF group), control-transfected myoblasts (control group), or medium only (medium group) was injected into syngeneic rat hearts 1 hour after left coronary artery occlusion. Myocardial VEGF-expression increased for 2 weeks in the VEGF group, resulting in enhanced angiogenesis without the formation of tumors. Grafted myoblasts had differentiated into multinucleated myotubes within host myocardium. Infarct size (33.3±1.4%, 38.1±1.4%, and 43.7±1.6% for VEGF, control, and medium groups, respectively; P =0.0005) was significantly reduced with VEGF treatment, and cardiac function improved in the VEGF group (maximum dP/dt: 4072.0±93.6, 3772.5±101.1, and 3482.5±90.6 mm Hg/s in the 3 groups, respectively; P =0.0011; minimum dP/dt: −504.2±68.5, −2311.3±57.0, and −2124.0±57.9 mm Hg/s, respectively; P =0.0008). Conclusions This combined strategy of cell transplantation with gene therapy could be of importance for the treatment of acute myocardial infarction.

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