Mechanisms Of Angiogenesis Research Articles

The use of the chorioallantoic membrane as an experimental model for studying markers of endometrial receptivity

The article presents a review of articles aimed at summarizing the results of studies using the choriollantoic membrane (СAM) to study markers and mechanisms of endometrial receptivity and angiogenesis. Considering these studies together clarifies the complex regulatory networks involved in vascular development and endometrial susceptibility. Understanding the intricacies of angiogenesis and endometrial susceptibility is crucial in reproductive medicine and infertility treatment. The chorioallantoic membrane (CAM) and its analogues, the angiogenic model derived from stroma (CAM), offer valuable platforms for such research. A comprehensive search of scientific literature databases was conducted to identify relevant studies using CAM. Studies using CAM have provided insight into markers of endometrial susceptibility, shedding light on structural changes associated with vascular development. Similarly, studies using CAM have provided valuable information on pinopods and other markers indicating endometrial susceptibility, indicating potential clinical applications in reproductive medicine. Together, these studies contribute to a deeper understanding of the cellular and molecular mechanisms of endometrial regulation. They emphasize the role of various factors, including growth factors, cytokines, and signaling pathways, in inducing endometrial angiogenesis and modulating its susceptibility. Such findings can serve as a basis for the development of new diagnostic and therapeutic strategies in reproductive medicine.

Isolation, culture, and characterization of primary endothelial cells and pericytes from mouse sciatic nerve.

The recovery of injured peripheral nerves relies on angiogenesis, where newly formed blood vessels act as pathways guiding Schwann cells across the wound to support axon regeneration. While some research has examined this process, the specific mechanisms of angiogenesis in peripheral nerve healing remain unclear. In vitro models are vital tools to investigate these mechanisms; however, no current in vitro culture methods exist for isolating vascular cells, such as endothelial cells (ECs) and pericytes, specifically from sciatic nerves. We developed a straightforward and reliable technique for isolating ECs and pericytes from injured sciatic nerves, optimized for use in in vitro studies. Cell types were characterized using specific markers and phenotypic assessments, with flow cytometry confirming cell identity and determining cell purity. Our method successfully isolated high-purity ECs and pericytes from injured sciatic nerves. Immunofluorescence analysis showed that primary cultured ECs exhibited strong positive staining for CD31, while pericytes stained strongly for NG2 and PDGFRβ. Flow cytometric analysis confirmed that ECs achieved a purity of 90.22%, and pericytes reached a purity of 92.01%. Both cell types were capable of forming organized capillary-like structures, and in co-culture systems, pericytes effectively wrapped around ECs. Current isolation methods for ECs and pericytes from sciatic nerves are limited. Although techniques exist for isolating these cells from other tissues, they often rely on enzymatic digestion, which can damage cell surface proteins and reduce cell viability. Our method allows for the efficient isolation of intact ECs and pericytes from sciatic nerve tissue without such drawbacks, providing a robust platform for in vitro studies. This newly developed method offers an effective approach to isolate ECs and pericytes from the sciatic nerve, contributing a valuable tool for investigating the function and pathology of angiogenesis in the context of sciatic nerve injury recovery.

LncRNA A1BG-AS1 regulates the progress of diabetic foot ulcers via sponging miR-214-3p

Nerve aberrations and vascular lesions in the distal lower limbs are the etiological factors for diabetic foot ulcers (DFUs). This study aimed to understand the regulatory mechanism of angiogenesis in patients with DFU by examining lncRNA, as well as to explore effective targets for diagnosing and treating DFU. The serum levels of A1BG-AS1 and miR-214-3p and the predictive power of A1BG-AS1 for DFU were determined by quantitative PCR and ROC analysis. The correlation of A1BG-AS1 with clinical characteristics was examined using chi-square tests. The risk factors for DFU in patients with type 2 diabetes mellitus (T2DM) were identified using the logistic regression model. Furthermore, the binding sites of A1BG-AS1 and miR-214-3p were determined. Next, A1BG-AS1 interference plasmid and miR-214-3p inhibitor were co-transfected into high glucose-induced cells to investigate their effects on the expression of angiogenesis-related genes and cell proliferation. The A1BG-AS1 levels were upregulated, whereas the miR-214-3p levels were downregulated in patients with DFU. The upregulation of A1BG-AS1 was significantly associated with both blood glucose levels and ulcer grades. A1BG-AS1 served as a crucial biomarker for diagnosing DFU and evaluating the risk of DFU occurrence in patients with T2DM. Co-transfection experiments revealed that the inhibition of miR-214-3p effectively recovered the suppressive effects of A1BG-AS1 on angiogenesis-related gene expression, endothelial cell differentiation, and proliferation. The sponging effect of A1BG-AS1 on miR-214-3p impaired angiogenesis in patients with DFU. Thus, A1BG-AS1 is a potential therapeutic target for DFU.

Type IV collagen expression is regulated by Notch3-mediated Notch signaling during angiogenesis.

Angiogenesis, the process of new blood vessel formation, involves endothelial cell proliferation and migration, accompanied by the remodeling of the extracellular matrix (ECM). Type IV collagen, a major ECM component, plays a critical role in vascular basement membrane regeneration, influencing cell polarity, migration, and survival. This study examines the regulatory role of Notch signaling, mediated by Notch3, in type IV collagen expression using TIG-1 fibroblasts and a co-culture angiogenesis model with human umbilical vein endothelial cells (HUVECs). Using small interfering RNA (siRNA) to suppress Notch3 expression, we observed a significant reduction in COL4A1 gene expression, which encodes the α1 chain of type IV collagen. Conversely, transient expression of the Notch3 intracellular domain (NICD3) activated Notch signaling, resulting in increased COL4A1 expression. In the co-culture model, pre-treatment of TIG-1cells with Notch signaling inhibitors, including siNotch3 and DAPT, decreased the number of α1(IV)-positive TIG-1 fibroblasts adjacent to HUVECs. This reduction highlights the essential role of Notch3-mediated signaling in promoting type IV collagen expression during angiogenesis. Our findings suggest that Notch signaling regulates type IV collagen expression levels, supporting basement membrane formation and vascular maturation. These results provide insight into the molecular mechanisms of angiogenesis, potentially contributing to therapeutic strategies targeting vascular-related pathologies.

Importance of vascularity and blood flow in the reproductive system of female birds: a review

<b><p>The reproductive system of female birds is characterized by a high metabolic rate associated with production of the egg constituents, i.e. the yolk in the ovary, and the albumen and calcified shell in the oviduct. Both organs require a high level of vascularization and intense blood flow, which differs depending on their activity. The increasing expansion of the vascular system and blood flow within the follicle wall as it develops facilitates the rapid delivery of oxygen, hormones, growth factors, nutrients, and egg-yolk precursors to the oocyte. The network of blood vessels is established during angiogenesis, a very complex process involving numerous regulators, the most important, of which are vascular endothelial growth factor and its receptors. Although angiogenesis is an essential process for the normal functioning of the female reproductive system, information about this event in birds is limited. This review aims to provide up-to-date information on the importance of proper vascularization, mechanisms of angiogenesis, and blood flow regulation within the reproductive system of hens. </b></p>

Exosomal miR-320d promotes angiogenesis and colorectal cancer metastasis via targeting GNAI1 to affect the JAK2/STAT3 signaling pathway

Colorectal cancer is a common malignant tumor, whose growth and metastasis are influenced by numerous factors. MicroRNAs have garnered increasing attention in recent years due to their involvement in tumor development. Exosomes are involved in intercellular signaling and influence tumor development by promoting tumor cell proliferation and metastasis through activation of angiogenesis and other mechanisms. This study aimed to investigate how the exosomes containing miR-320d from colorectal cancer (CRC) cells promote colorectal cancer metastasis by regulating angiogenesis. CRC-derived exosomes containing miR-320d can be transferred to vascular endothelial cells, facilitating their proliferation, invasion, migration, and angiogenesis. By targeting GNAI1, miR-320d in these exosomes reduces GNAI1 levels in endothelial cells, causing more JAK2/STAT3 activation and VEGFA production. This ultimately enhances the migration and angiogenic capacity of vascular endothelial cells. Moreover, CRC patients with high levels of miR-320d in their blood respond better to treatment with bevacizumab. In vivo experiments further proved the role of miR-320d from CRC exosomes in increasing tumor size, blood vessel formation, and the spread of cancer to the liver. In this study, we have demonstrated that exosomal miR-320d promotes cancer cell metastasis and enhances angiogenesis by downregulating GNAI1 expression and enhancing JAK2/STAT3.

Angiogenic and neurogenic potential of dental-derived stem cells for functional pulp regeneration: A narrative review.

Dental pulp tissue engineering is expected to become an ideal treatment for irreversible pulpitis and apical periodontitis. However, angiogenesis and neurogenesis for functional pulp regeneration have not yet met the standard for large-scale clinical application, and need further research. This review focused on the potential mechanisms of angiogenesis and neurogenesis in pulp regeneration, including stem cell types, upstream and downstream regulatory molecules and cascade signalling pathways, thereby providing a theoretical basis and inspiring new ideas to improve the effectiveness of dental pulp tissue engineering. An electronic literature search was carried out using the keywords of 'pulp regeneration', 'stem cell transplantation', 'dental pulp stem cells', 'angiogenesis' and 'neurogenesis'. The resulting literature was screened and reviewed. Stem cells used in dental pulp tissue engineering can be classified as dental-derived and non-dental-derived stem cells, amongst which dental pulp stem cells (DPSC) have achieved promising results in animal experiments and clinical trials. Multiple molecules and signalling pathways are involved in the process of DPSC-mediated angiogenic and neurogenetic regeneration. In order to promote angiogenesis and neurogenesis in pulp regeneration, feasible measures include the addition of growth factors, the modulation of transcription factors and signalling pathways, the use of extracellular vesicles and the modification of bioscaffold materials. Dental pulp tissue engineering has had breakthroughs in preclinical and clinical studies invivo. Overcoming difficulties in pulpal angiogenesis and neurogenesis, and achieving functional pulp regeneration will lead to a significant impact in endodontics.

Progress on angiogenic and antiangiogenic agents in the tumor microenvironment.

The development of tumors and their metastasis relies heavily on the process of angiogenesis. When the volume of a tumor expands, the resulting internal hypoxic conditions trigger the body to enhance the production of various angiogenic factors. These include vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), and transforming growth factor-α (TGF-α), all of which work together to stimulate the activation of endothelial cells and catalyze angiogenesis. Antiangiogenic therapy (AAT) aims to normalize tumor blood vessels by inhibiting these angiogenic signals. In this review, we will explore the molecular mechanisms of angiogenesis within the tumor microenvironment, discuss traditional antiangiogenic drugs along with their limitations, examine new antiangiogenic drugs and the advantages of combination therapy, and consider future research directions in the field of antiangiogenic drugs. This comprehensive overview aims to provide insights that may aid in the development of more effective anti-tumor treatments.

CEP70 in Prostate Cancer: A Novel Mechanism of Angiogenesis and Metastasis through Upregulation of Vascular Endothelial Growth Factor A Expression.

This study aims to investigate centrosomal protein 70 (CEP70) in prostate cancer and its effects on angiogenesis and tumour metastasis and elucidate its molecular mechanisms. We evaluated CEP70 and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) in tissue samples from patients with prostate cancer by immunohistochemistry. In vitro experiments included overexpressing CEP70 through transfection and assessing its impact on human umbilical vein endothelial cells (HUVECs). Intervention experiments with an NF-κB pathway inhibitor were conducted to verify the mechanism. Finally, the effects of CEP70 on tumour growth, angiogenesis and metastasis were examined in a nude mouse model. CEP70 was significantly overexpressed in prostate cancer tissues compared with that in adjacent normal tissues (p < 0.001). In vitro experiments demonstrated that CEP70 overexpression promoted HUVEC migration (p < 0.001), invasion (p < 0.001) and tube formation (p < 0.05). CEP70 significantly upregulated VEGFA expression in prostate cancer cells at messenger RNA (mRNA) (p < 0.001) and protein levels (p < 0.05). VEGFA knockdown experiments confirmed CEP70 as an essential cytokine for CEP70-induced angiogenesis (p < 0.01). Mechanistically, CEP70 promoted VEGFA expression by activating the NF-κB signalling pathway, as evidenced by the reversal of CEP70-induced effects upon treatment with the NF-κB inhibitor BAY11-7082 (p < 0.01). CEP70 promotes tumour angiogenesis and metastasis by upregulating VEGFA through NF-κB pathway activation.

PDPN/CCL2/STAT3 feedback loop alter CAF heterogeneity to promote angiogenesis in colorectal cancer.

Colorectal cancer (CRC) is one of the common clinical malignancies and the fourth leading cause of cancer-related death in the world. The tumor microenvironment (TME) plays a crucial role in promoting tumor angiogenesis, and cancer-associated fibroblasts (CAFs) are one of the key components of the tumor microenvironment. However, due to the high heterogeneity of CAFs, elucidating the molecular mechanism of CAF-mediated tumor angiogenesis remained elusive. In our study, we found that there is pro-angiogenic functional heterogeneity of CAFs in colorectal cancer and we clarified that Podoplanin (PDPN) can specifically label CAF subpopulations with pro-angiogenic functions. We also revealed that PDPN + CAF could maintain CAF heterogeneity by forming a PDPN/CCL2/STAT3 feedback loop through autocrine CCL2, while activate STAT3 signaling pathway in endothelial cells to promote angiogenesis through paracrine CCL2. We demonstrated WP1066 could inhibit colorectal cancer angiogenesis by blocking both the PDPN/CCL2/STAT3 feedback loop in CAFs and the STAT3 signaling pathway in endothelial cells. Altogether, our study suggests that STAT3 could be a potential therapeutic target for blocking angiogenesis in colorectal cancer. We provide theoretical basis and new therapeutic strategies for the clinical treatment of colorectal cancer.

Exploring the role of angiogenesis in fibrosis and malignant transformation in oral submucous fibrosis: a systematic review and meta-analysis.

Angiogenesis is a crucial molecular driver of fibrosis in various inflammatory lesions. Oral submucous fibrosis (OSMF) is a chronic inflammatory fibrotic disorder with malignant potential. The angiogenetic pathways in OSMF remain obscure due to limited research, necessitating an in-depth review. This review aimed to illuminate the cryptic pathogenetic mechanisms of angiogenesis in the disease progression/fibrosis of OSMF and its malignant transformation, providing insights for improved treatment. Extensive literature searches were conducted across an array of databases until October 2023. Original research articles on angiogenesis in OSMF were included, and the risk of bias was assessed using the modified Newcastle-Ottawa scale. RevMan ver. 5.4 (Cochrane Collaboration) was used for data analysis. Thirty-four articles were included for qualitative synthesis and seven for quantitative analysis. Findings revealed that angiogenesis was significantly increased in early-stage OSMF but decreased as the disease advanced. It was also associated with the severity of epithelial dysplasia and malignant transformation. A random-effects model confirmed the upregulation of angiogenesis as a significant risk factor in early-stage fibrosis and malignant transformation. The mounting evidence reinforces that angiogenesis plays a crucial role in the progression of early-stage fibrosis of OSMF and its malignant transformation, opening avenues for diagnostic and therapeutic interventions.

CSWT improves ventricular function by promoting angiogenesis through Rho/ROCK/ERK1/2 signal pathway in infarcted myocardium in rats

Abstract Objective This study aimed to investigate the effects of extracorporeal cardiac shock wave therapy (CSWT) on myocardial ischemia and cardiac function in rats with myocardial infarction, and to explore its impact on the expression of myocardial vascular endothelial growth factor and the extent of myocardial fibrosis, thereby elucidating the mechanism of angiogenesis. Methods A rat model of myocardial infarction was induced by ligating the left anterior descending branch of the coronary artery, confirmed by echocardiography. Animals were randomly assigned to five groups: sham operation group, myocardial infarction group, myocardial infarction + CSWT group, myocardial infarction + Y-27632 group, and myocardial infarction + CSWT + Y-27632 group. Cardiac function was evaluated by echocardiography on the 16th and 72nd day post-surgery. Myocardial morphology was assessed by HE staining, and the extent of myocardial fibrosis was determined by Masson's trichrome staining. Immunohistochemical staining for factor VIII was conducted to observe angiogenesis in each infarcted area. Western blotting was employed to detect the protein expression of extracellular regulated kinase (ERK1/2) and pro-angiogenic cytokines in the infarct border zone. Results CSWT treatment significantly reduced myocardial fibrosis and improved cardiac function compared to the myocardial infarction group. Additionally, CSWT upregulated ERK expression and angiogenesis-related factors, promoting angiogenesis. The beneficial effects of CSWT were abolished by inhibiting the Rho/ROCK/ERK1/2 pathway. Furthermore, the area of myocardial fibrosis was significantly reduced in the MI+Y-27632 group compared to the myocardial infarction group (p &amp;lt; 0.01), and left ventricular systolic function index was significantly higher in the myocardial infarction group. Conclusions CSWT may promote angiogenesis post-myocardial infarction by activating the Rho/ROCK/ERK1/2 pathway. Additionally, Y-27632 may improve cardiac function in rats with myocardial infarction, potentially through mitigating myocardial fibrosis.echo images of ratsprotein expression by WB

The potential role of Ral-interacting protein 76 and vascular endothelial growth factor on angiogenesis in the tumor and ovarian corpus luteum microenvironment.

Tumors and the ovarian corpus luteum have complex mechanisms in the growth microenvironment. Angiogenesis is especially important for demonstrating the molecular mechanism of dynamic cellular function in tumors and corpus luteum. Angiogenesis in tumors and corpus luteum seems to have a similar function, and Ral-interacting protein 76 (RLIP76) and vascular endothelial growth factor (VEGF) are expressed in the tissues of tumors and ovarian corpus luteum. RLIP76 is a potential factor with VEGF in the tumor and corpus luteum angiogenesis. RLIP76 regulates a small GTPase (R-Ras) in cell survival, spreading, and migration. VEGF activates angiogenic functions in tumor and endothelial cells. Hypoxia-inducible factor-1 (HIF-1) is important in tumor growth, tumor angiogenesis, and corpus luteum. VEGF and HIF-1 regulate the angiogenic function of RLIP76, and RLIP76 controls vascular growth in endothelial and tumor cells. RLIP76, R-Ras, VEGF, and HIF-1 may be useful in the research of corpus luteum and cancer therapy and the study of mechanisms of tumor and corpus luteum angiogenesis. This review will help to elucidate the roles of RLIP76 and VEGF in tumor and corpus luteum angiogenesis, tumorigenesis, and the specific regulation of RLIP76 and VEGF. Thus, we reviewed the potential role of RLIP76 and VEGF in the angiogenesis of the tumor and corpus luteum in the tumor and ovarian microenvironment.

14K prolactin derived 14-mer antiangiogenic peptide targets bradykinin-/nitric oxide-cGMP-dependent angiogenesis.

Over the past few decades, VEGF-targeted antiangiogenic therapy for cancers has gained increasing attention. Nevertheless, there are still several limitations such as the potential resistance mechanisms arising in cancer cells against these therapies and their potential adverse effects. These limitations highlight the need for novel anti-angiogenesis molecules and better understanding of the mechanisms of tumor angiogenesis. In the present study, we investigated the antiangiogenic properties of a novel 14-mer antiangiogenic peptide (14-MAP) derived from N-terminal 14 kDa buffalo prolactin and characterized its mode of action. 14-MAP at the picomolar concentration inhibited VEGF- and bradykinin (an autacoid peptide expressed in vascular tissues in pathophysiology, BK)-stimulated endothelial nitric oxide (eNO) production, cell migration, and proliferation in endothelial cells and vessel development in the chick embryo. Although this peptide inhibited both VEGF- and BK-dependent angiogenic processes, its action was more pronounced in the latter. Moreover, the interference of 14-MAP with the eNO synthase (eNOS)-cyclic GMP pathway was also identified. A combination of a low dose of Avastin, a widely used drug targeting VEGF-dependent angiogenesis, and 14-MAP significantly reduced tumor size in an in vivo model of human colon cancer. Taken together, our results suggest that 14-MAP, a BK- and eNOS-dependent antiangiogenic peptide, might be useful for overcoming the limitation of VEGF-targeted antiangiogenic therapy in cancer patients. However, further studies will be required to further characterize its mode of action and therapeutic potential.

Combination of JAKi and HDACi Exerts Antiangiogenic Potential in Cutaneous T-Cell Lymphoma.

Angiogenesis plays a pivotal role in the growth and metastasis of tumors, including the development and progression of cutaneous lymphomas. The chick embryo CAM model has been utilized in various studies to assess the growth rate, angiogenic potential, and metastatic capability of different tumor types and malignant cell lines. However, the precise mechanisms of angiogenesis in CTCL and the influence of Ruxolitinib or Resminostat on angiogenesis in hematological malignancies and solid tumors are not well understood. Recent in vitro and in vivo data have demonstrated the synergistic inhibition of tumorigenesis and metastasis in experimental models of CTCL when using the combination of Resminostat (HDACi) with Ruxolitinib (JAKi). The present work aims to elucidate the effects of this combination on the tumor microenvironment's vascular components. We investigated the effects of Ruxolitinib (JAKi) in combination with Resminostat (HDACi) treatment in transendothelial migration of CTCL cells (106 MyLa and SeAx) by using a transwell-based transendothelial migration assay and tumor angiogenesis in vivo. We used the CTCL chick embryo CAM model with xenografted tumors derived from implanted MyLa and SeAx cells and administered topically 15 μM ruxolitinib and 5 μM Resminostat every two days during a 5-day period. JAKi and HDACi inhibited CTCL cell transendothelial migration by 75% and 82% (p < 0.05) in both CTCL engrafted cells (MyLa and SeAx, respectively) compared to the untreated group. Moreover, the combination of ruxolitinib with resminostat blocked angiogenesis by significantly reducing the number of blood vessel formation by 49% and 34% in both MyLa and SeAx, respectively (p < 0.05), indicating that the proposed combination exerted significant anti-angiogenic effects in the CAM CTCL model. Overall, these data provide valuable insights into potential therapeutic strategies targeting angiogenesis in CTCL, paving the way for more effective treatment approaches in the future.

Targeted anti-angiogenesis therapy for advanced osteosarcoma.

To date, despite extensive research, the prognosis of advanced osteosarcoma has not improved significantly. Thus, patients experience a reduced survival rate, suggesting that a reevaluation of current treatment strategies is required. Recently, in addition to routine surgery, chemotherapy and radiotherapy, researchers have explored more effective and safer treatments, including targeted therapy, immunotherapy, anti-angiogenesis therapy, metabolic targets therapy, and nanomedicine therapy. The tumorigenesis and development of osteosarcoma is closely related to angiogenesis. Thus, anti-angiogenesis therapy is crucial to treat osteosarcoma; however, recent clinical trials found that it has insufficient efficacy. To solve this problem, the causes of treatment failure and improve treatment strategies should be investigated. This review focuses on summarizing the pathophysiological mechanisms of angiogenesis in osteosarcoma and recent advances in anti-angiogenesis treatment of osteosarcoma. We also discuss some clinical studies, with the aim of providing new ideas to improve treatment strategies for osteosarcoma and the prognosis of patients.

Enhancing Bone Healing Through Localized Cold Therapy in a Murine Femoral Fracture Model.

Fracture healing, a critical and complex biological process, often presents challenges in clinical practice with the current standards failing to fully address the medical needs for rapid and effective recovery. In this work, a localized cold therapy is investigated as an alternative approach to expedite bone healing. We hypothesized that optimized cold application can enhance bone healing within a fracture model by inducing hypoxia, leading to accelerated angiogenesis along with improved osteogenesis. A short, localized cold exposure is directly applied to the fracture site over a 4-week period in a mouse fracture model, aiming to assess its impact on bone formation through mechanisms of angiogenesis and osteogenesis. Our results revealed a significantly greater volume of new bone tissue and enhanced vascularity at the fracture site in the cold-treated group compared with controls. Calcified tissue histology analysis showed that the accelerated callus maturation and development of the vascular network following cold exposure were associated with an activity increase of alkaline phosphatase and transient receptor potential vanilloid 1. These biological changes were accompanied by a hypoxic environment induced during cold therapy. The study provides compelling evidence supporting the efficacy of intermittent cold therapy in accelerating fracture healing. These promising results highlight the need for further research in larger-scale studies and diverse fracture models, underlining the potential of cold therapy as a novel, noninvasive treatment strategy in orthopedic care.

New Interpretations for Sprouting, Intussusception, Ansiform, and Coalescent Types of Angiogenesis.

Angiogenesis, or the development of blood vessels by growing from already-formed vessels, is observed in embryonic development, physiological cyclical processes such as wound healing, the encapsulation of foreign bodies, tumor growth, and some other situations. In this review, we analyze the cellular mechanisms of angiogenesis, namely, angiogenesis by sprouting, ansiform (by loop formation) angiogenesis, coalescent angiogenesis, and angiogenesis by intussusception (splitting the capillary into two channels). The analysis of data revealed a lot of unanswered questions and contradictions. Here, we propose several new models of angiogenesis explaining these contradictions.

Angiogenesis in psoriasis as a therapeutic target (literature review)

One of the characteristic features of psoriasis is increased vascularization in the psoriatic plaque. It is known that this process occurs as a result of pathological angiogenesis, which leads to an increase of blood vessels in the lesion, increased proliferation of endothelial cells, vasodilation and increased permeability of the vascular wall, facilitating penetration of immune cells and increasing inflammation. Many signaling molecules are involved in the process of angiogenesis in psoriasis. The most important indicator of the severity of pathological angiogenesis is endothelial vascular growth factor (VEGF). The issue of using blood serum analysis for endothelial vascular growth factor (VEGF) and diagnostic imaging techniques of the vascular network in psoriatic plaques to determine the severity of the process and the possibility of using additional treatment directions aimed at reducing vascularization is being considered. At the moment, the mechanisms of angiogenesis in psoriasis are being actively studied, and the possibilities of therapeutic influence on this link of pathogenesis are especially interesting. The authors present an analysis of the current literature on this topic, and suggest possible available treatment strategies based on the data obtained. Further research in this direction is needed to optimize the therapy of psoriasis, the main purpose of which will be to reduce the duration of treatment and prolong the time of remission.

Abstract Tu023: The VEGF-A splice variants as a mechanism of impaired Inflammatory Angiogenesis in the context of advanced aging.

Background and Objectives: Aging and age-related diseases like peripheral artery disease (PAD) is associated with impairment of angiogenesis responses to injury. Critical ischemic limb and wound injury animal models have shown impact of monocytes/macrophages as a major source of angiogenic mediators leading to new arterial growth. Aging has also been associated with impairment of blood flow recovery and reduced VEGF-A expression in animals. However, recombinant VEGF-A administration or clinical trials involving VEGF-A have not fully overcome the foot perfusion and prevent limb/leg amputation. We sought to understand molecular mechanisms of reduced VEGF-A expression which remain incomplete in the context of advanced aging. Results: Firstly, in hindlimb ischemia mouse model, our data from liposomes containing-clodronate treated mice (12-weeks C57Bl6 with macrophage depletion model ) ( Fig. 1a ) demonstrate impairment of blood flow recovery compared to Control group. On day 3 post-surgery, VEGF-A and VEGF-A isoforms expression (VEGF-A 165 a and VEGF-A 165 b, respectively) were reduced in ischemic muscle. Fluorescence staining showed a reduction of macrophages (CD68 + ) was also associated with reduced endothelial cells (CD31 + ). Using a myeloid-specific and inducible deleted VEGF fl/fl mice, we then have shown a key role of early inflammatory macrophages stage as a major source of VEGF-A required for angiogenesis in young mice (Fig. 1b). Secondly, bone marrow-derived-macrophages (BMDMs) from C57Bl6 104-weeks mice also demonstrate reduced VEGF-A expression. Aged BMDMs demonstrate reduced VEGF-A 165 a while VEGF-A 165 b was highly increased. Polarized BMDMs from 12-weeks demonstrate increased VEGFR1 in “M2" macrophages while VEGFR2 was increased in “M1” macrophages. On the other hand, BMDMs from 104-weeks demonstrate reduced VEGFR2 expression while VEGFR1 was unaffected compared to young. Lastly, 104-weeks mice also demonstrate severe impairment of blood flow recovery ( Fig. 2 ) after surgery and reduced VEGF-A and VEGF-A 165 a in ischemic muscle tissue. VEGF-A 165 b was increased and both receptors, VEGF-R1/R2 levels ( Fig. 3 ) were also reduced. Fluorescence staining on day 3 post ligation demonstrates reduced endothelial cells recruitment in muscle tissue while macrophage (CD68+) number was similar. Conclusion: Our investigations will contribute to define mechanisms whereby vascular injury is associated with VEGF-A isoforms specific switch in the context of advanced aging.