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FASEB Journal : Official Publication of... Dec 2019M3 is a broad-spectrum chemokine-binding protein that inactivates inflammatory chemokines, including CCL2, CCL5, and CXCL1. The aim of this study was to compare whether...
M3 is a broad-spectrum chemokine-binding protein that inactivates inflammatory chemokines, including CCL2, CCL5, and CXCL1. The aim of this study was to compare whether M3 could inhibit angiogenesis driven by inflammation or ischemia. Here, apolipoprotein E mice were injected with adenoviral M3 (AdM3) or control adenoviral green fluorescent protein (AdGFP) 3 d prior to stimulating angiogenesis using 2 established models that distinctly represent inflammatory or ischemia-driven angiogenesis, namely the periarterial femoral cuff and hind limb ischemia. AdM3 reduced intimal thickening, adventitial capillary density, and macrophage accumulation in femoral arteries 21 d after periarterial femoral cuff placement compared with AdGFP-treated mice ( < 0.05). AdM3 also reduced mRNA expression of proangiogenic VEGF, inflammatory markers IL-6 and IL-1β, and vascular smooth muscle cell (VSMC)-activated synthetic markers Krüppel-like family of transcription factor 4 (KLF4) and platelet-derived growth factor receptor β (PDGFRβ) in the inflammatory cuff model. In contrast, capillary density, VSMC content, blood flow perfusion, and VEGF gene expression were unaltered between groups in skeletal muscle following hind limb ischemia. , AdM3 significantly reduced human microvascular endothelial cell 1 proliferation, migration, and tubule formation by ∼17, 71.3, and 8.7% ( < 0.05) in macrophage-conditioned medium associating with reduced VEGF and hypoxia-inducible factor 1α mRNA but not in hypoxia (1% O). Compared with AdGFP, AdM3 also inhibited VSMC proliferation and migration and reduced mRNA expression of KLF4 and PDGFRβ under inflammatory conditions. In contrast, AdM3 had no effect on VSMC processes in response to hypoxia . Our findings show that broad-spectrum inhibition of inflammatory chemokines by M3 inhibits inflammatory-driven but not ischemia-driven angiogenesis, presenting a novel strategy for the treatment of diseases associated with inflammatory-driven angiogenesis.-Ravindran, D., Cartland, S. P., Bursill, C. A., Kavurma, M. M. Broad-spectrum chemokine inhibition blocks inflammation-induced angiogenesis, but preserves ischemia-driven angiogenesis.
Topics: Adenoviridae; Animals; Cell Movement; Cell Proliferation; Chemokines; Hindlimb; Hypoxia; Inflammation; Ischemia; Kruppel-Like Factor 4; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout, ApoE; Muscle, Skeletal; Neovascularization, Pathologic; Regional Blood Flow; Signal Transduction; Viral Proteins
PubMed: 31574232
DOI: 10.1096/fj.201900232RR -
Experimental Cell Research Nov 2021Angiogenesis plays a pivotal role in cancer initiation, maintenance, and progression. Diet may inhibit, retard or reverse these processes affecting angiogenesis... (Review)
Review
Angiogenesis plays a pivotal role in cancer initiation, maintenance, and progression. Diet may inhibit, retard or reverse these processes affecting angiogenesis (angioprevention). Nutraceuticals, such as omega-3 fatty acids, amino acids, proteins, vitamins, minerals, fibers, and phenolic compounds, improve health benefits as they are a source of bioactive compounds that, among other effects, can regulate angiogenesis. The literature concerning the pro-angiogenic and/or anti-angiogenic nutraceuticals and the possible activated pathways in cancer and other non-neoplastic diseases by in vivo and in vitro experiments are reviewed.
Topics: Angiogenesis Inhibitors; Dietary Supplements; Humans; Immunotherapy; Neoplasms; Neovascularization, Pathologic
PubMed: 34637764
DOI: 10.1016/j.yexcr.2021.112859 -
Bio/technology (Nature Publishing... Jul 1991Angiogenesis, the formation of new capillaries, is essential to a number of important physiological events, both normal and pathological. Recently, increased attention... (Review)
Review
Angiogenesis, the formation of new capillaries, is essential to a number of important physiological events, both normal and pathological. Recently, increased attention has focused on the purification and characterization of inhibitors of this process, because of the potential therapeutic value of angiogenesis inhibitors in controlling such "angiogenic diseases" as proliferative retinopathy, solid tumors, rheumatoid arthritis, and neovascular glaucoma. We review the process of neovascularization and the assays that have been developed to study its inhibition in vivo and in vitro. We also discuss the properties of different angiogenesis inhibitors and examine the mechanisms by which such inhibitors could potentially intervene in the process of neovascularization.
Topics: Animals; Humans; Neovascularization, Pathologic
PubMed: 1370057
DOI: 10.1038/nbt0791-630 -
Current Opinion in Rheumatology Sep 2008Much has been documented in recent years on the possible involvement of angiogenesis in osteoarthritis. An understanding of the various regulatory mechanisms controlling... (Review)
Review
PURPOSE OF REVIEW
Much has been documented in recent years on the possible involvement of angiogenesis in osteoarthritis. An understanding of the various regulatory mechanisms controlling blood vessel growth in the joint should lead to novel therapeutics, which selectively inhibit undesirable angiogenesis. Here, we summarize recent findings on the roles of angiogenesis in osteoarthritis and place this evidence in the context of previous literature in order to help explain pain and disease progression.
RECENT FINDINGS
Inflammation and angiogenesis are closely associated in osteoarthritis, modulating functions of chondrocytes, contributing towards abnormal tissue growth and perfusion, ossification and endochondral bone development, leading to radiographic changes observed in the joint. Innervation accompanies vascularization and inflammation, hypoxia and mechanical overload are all thought to contribute in sensitizing these new nerves leading to increased pain. Articular cartilage provides a unique environment in which blood vessel growth is regulated by endogenous angiogenesis inhibitors and matrix constituents, as well as by growth factors produced by chondrocytes, subchondral bone and synovium. MRI and ultrasound enable the in-vivo visualization of abnormal vascularity in synovium and subchondral bone that have not been apparent with conventional radiography. As a result of these new findings, the widely accepted notion that osteoarthritis is primarily a disease of the cartilage is being challenged.
SUMMARY
Molecular mechanisms and consequences of angiogenesis in osteoarthritis are slowly being elucidated. Studies, both in humans and animal models, support the notion that inhibiting angiogenesis will provide effective therapeutic strategies for treating osteoarthritis. Better techniques that can more precisely visualize the vascular changes of the whole joint can further enhance our understanding of osteoarthritis, and can provide proof of concept and early evidence of efficacy in trials of novel therapeutic interventions.
Topics: Animals; Humans; Neovascularization, Pathologic; Osteoarthritis
PubMed: 18698180
DOI: 10.1097/BOR.0b013e3283103d12 -
The Keio Journal of Medicine Mar 2022The uncontrolled growth of blood vessels is a major pathological factor in human eye diseases that can result in blindness. This effect is termed ocular... (Review)
Review
The uncontrolled growth of blood vessels is a major pathological factor in human eye diseases that can result in blindness. This effect is termed ocular neovascularization and is seen in diabetic retinopathy, age-related macular degeneration, glaucoma and retinopathy of prematurity. Current treatments for these diseases include laser photocoagulation, topical injection of corticosteroids, intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents and vitreoretinal surgery. Although strategies to inhibit VEGF have proved to be dramatically successful in some clinical studies, there remains the possibility of significant adverse effects regarding the blockade of crucial physiological roles of VEGF and the invasive nature of the treatments. Moreover, it is evident that other pro-angiogenic factors also play important roles in the development of these diseases, as seen in cases in which anti-VEGF therapies have failed. Therefore, new types of effective treatments are required. In this review, we discuss a promising strategy for the treatment of ocular neovascular diseases, i.e., the inhibition of hypoxia-inducible factor (HIF), a master regulator of angiogenesis. We also summarize promising recently investigated HIF inhibitors as treatments for ocular diseases. This review will facilitate more comprehensive approaches to understanding the protective aspects of HIF inhibition in the prevention of ocular diseases.
Topics: Eye; Humans; Infant, Newborn; Macular Degeneration; Neovascularization, Pathologic; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
PubMed: 33840673
DOI: 10.2302/kjm.2021-0004-IR -
Journal of the National Medical...Rheumatoid arthritis (RA) is a chronic inflammatory disease with a serious pre-vascular inflammatory phase, followed by significant increase in vessel growth. Inhibition... (Review)
Review
Rheumatoid arthritis (RA) is a chronic inflammatory disease with a serious pre-vascular inflammatory phase, followed by significant increase in vessel growth. Inhibition of angiogenesis is a novel therapeutic strategy against RA. The Chinese herbal remedy Tripterygium wilfordii, Hook. f. (TwHf) has been reported to be therapeutically efficacious in the treatment of RA. Recent studies have revealed that treatment with TwHf extracts inhibit angiogenesis of RA, thereby elaborately attenuation RA symptom. This review mainly addresses the anti-angiogenesis effect of TwHf in treatment of RA.
Topics: Angiogenesis Inhibitors; Antirheumatic Agents; Arthritis, Rheumatoid; Drugs, Chinese Herbal; Humans; Neovascularization, Pathologic; Phytotherapy; Treatment Outcome; Tripterygium
PubMed: 28599756
DOI: 10.1016/j.jnma.2017.02.007 -
Antioxidants & Redox Signaling Oct 2002Reactive oxygen species (ROS) play a crucial role in vascular angiogenesis. Both in vitro and in vivo studies indicate that angiogenic response in vascular tissue is... (Review)
Review
Reactive oxygen species (ROS) play a crucial role in vascular angiogenesis. Both in vitro and in vivo studies indicate that angiogenic response in vascular tissue is triggered by ROS signaling in a highly coordinated manner. It appears that massive amounts of ROS produced during ischemia and reperfusion in the vascular tissue, especially in heart, cause significant injury to the cardiomyocyte and endothelial cells. However, during the reperfusion, the same ROS potentiates a repair process and triggers a signal transduction cascade leading to angiogenesis. Although several other factors are likely to be involved for such angiogenic response, ROS certainly plays a crucial role as evident from its direct role as mediator of angiogenesis and inhibition of angiogenesis with free radical scavengers and/or antioxidants. Angiogenesis is regulated by redox-sensing transcription factors such as nuclear factor-kappaB, and oxidants such as hydrogen peroxide and free radicals, such as nitric oxide may function as second messengers in this highly coordinated process. Furthermore, expression of many angiogenic genes including those for vascular endothelial growth factor, fibroblast growth factor, platelet-derived growth factor, and receptors such as Flt-1, Flk-1, Ang-1, and Ang-2 are likely to be regulated by redox signaling. It is tempting to speculate that the angiogenic response is under the autocrine and/or paracrine control of one or more cytokines, which in turn is redox-regulated. Through angiogenesis, ROS appear to pave the way of repairing the vascular tissues that have been damaged during ischemia and reperfusion.
Topics: Animals; Antioxidants; Free Radical Scavengers; Growth Substances; Humans; Ischemia; Neovascularization, Pathologic; Neovascularization, Physiologic; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Reperfusion Injury; Signal Transduction
PubMed: 12470509
DOI: 10.1089/152308602760598963 -
Cellular and Molecular Life Sciences :... Jun 2022All living beings continue their life by receiving energy and by excreting waste products. In animals, the arteries are the pathways of these transfers to the cells.... (Review)
Review
All living beings continue their life by receiving energy and by excreting waste products. In animals, the arteries are the pathways of these transfers to the cells. Angiogenesis, the formation of the arteries by the development of pre-existed parental blood vessels, is a phenomenon that occurs naturally during puberty due to certain physiological processes such as menstruation, wound healing, or the adaptation of athletes' bodies during exercise. Nonetheless, the same life-giving process also occurs frequently in some patients and, conversely, occurs slowly in some physiological problems, such as cancer and diabetes, so inhibiting angiogenesis has been considered to be one of the important strategies to fight these diseases. Accordingly, in tissue engineering and regenerative medicine, the highly controlled process of angiogenesis is very important in tissue repairing. Excessive angiogenesis can promote tumor progression and lack of enough angiogensis can hinder tissue repair. Thereby, both excessive and deficient angiogenesis can be problematic, this review article introduces and describes the types of factors involved in controlling angiogenesis. Considering all of the existing strategies, we will try to lay out the latest knowledge that deals with stimulating/inhibiting the angiogenesis. At the end of the article, owing to the early-reviewed mechanical aspects that overshadow angiogenesis, the strategies of angiogenesis in tissue engineering will be discussed.
Topics: Animals; Humans; Neovascularization, Pathologic; Neovascularization, Physiologic; Regenerative Medicine; Tissue Engineering; Wound Healing
PubMed: 35672585
DOI: 10.1007/s00018-022-04348-5 -
Journal of Cerebral Blood Flow and... Aug 201920-HETE, an arachidonic acid metabolite synthesized by cytochrome P450 4A, plays an important role in acute brain damage from ischemic stroke or subarachnoid hemorrhage....
20-HETE, an arachidonic acid metabolite synthesized by cytochrome P450 4A, plays an important role in acute brain damage from ischemic stroke or subarachnoid hemorrhage. We tested the hypothesis that 20-HETE inhibition has a protective effect after intracerebral hemorrhage (ICH) and then investigated its effect on angiogenesis. We exposed hippocampal slice cultures to hemoglobin and induced ICH in mouse brains by intrastriatal collagenase injection to investigate the protective effect of 20-HETE synthesis inhibitor N-hydroxy-N'-(4--butyl-2-methylphenyl)-formamidine (HET0016). Hemoglobin-induced neuronal death was assessed by propidium iodide after 18 h in vitro. Lesion volume, neurologic deficits, cell death, reactive oxygen species (ROS), neuroinflammation, and angiogenesis were evaluated at different time points after ICH. In cultured mouse hippocampal slices, HET0016 attenuated hemoglobin-induced neuronal death and decreased levels of proinflammatory cytokines and ROS. In vivo, HET0016 reduced brain lesion volume and neurologic deficits, and decreased neuronal death, ROS production, gelatinolytic activity, and the inflammatory response at three days after ICH. However, HET0016 did not inhibit angiogenesis, as levels of CD31, VEGF, and VEGFR2 were unchanged on day 28. We conclude that 20-HETE is involved in ICH-induced brain damage. Inhibition of 20-HETE synthesis may provide a viable means to mitigate ICH injury without inhibition of angiogenesis.
Topics: Animals; Cerebral Hemorrhage; Enzyme Inhibitors; Hydroxyeicosatetraenoic Acids; Male; Mice; Mice, Inbred C57BL; Neovascularization, Physiologic
PubMed: 29485354
DOI: 10.1177/0271678X18762645 -
Cancer Letters Jun 2015Selective estrogen receptor modulators (SERM) including tamoxifen are known to inhibit angiogenesis. However, the underlying mechanism, which is independent of their...
Selective estrogen receptor modulators (SERM) including tamoxifen are known to inhibit angiogenesis. However, the underlying mechanism, which is independent of their action on the estrogen receptor (ER), has remained largely unknown. In the present study, we found that tamoxifen and other SERM inhibited cholesterol trafficking in endothelial cells, causing a hyper-accumulation of cholesterol in late endosomes/lysosomes. Inhibition of cholesterol trafficking by tamoxifen was accompanied by abnormal subcellular distribution of vascular endothelial growth factor receptor-2 (VEGFR2) and inhibition of the terminal glycosylation of the receptor. Tamoxifen also caused perinuclear positioning of lysosomes, which in turn trapped the mammalian target of rapamycin (mTOR) in the perinuclear region of endothelial cells. Abnormal distribution of VEGFR2 and mTOR and inhibition of VEGFR2 and mTOR activities by tamoxifen were significantly reversed by addition of cholesterol-cyclodextrin complex to the culture media of endothelial cells. Moreover, high concentrations of tamoxifen inhibited endothelial and breast cancer cell proliferation in a cholesterol-dependent, but ER-independent, manner. Together, these results unraveled a previously unrecognized mechanism of angiogenesis inhibition by tamoxifen and other SERM, implicating cholesterol trafficking as an attractive therapeutic target for cancer treatment.
Topics: Angiogenesis Inhibitors; Breast Neoplasms; Cholesterol; Estrogen Antagonists; Female; Human Umbilical Vein Endothelial Cells; Humans; MCF-7 Cells; Neovascularization, Pathologic; Neovascularization, Physiologic; Receptors, Estrogen; Selective Estrogen Receptor Modulators; Tamoxifen; Triple Negative Breast Neoplasms
PubMed: 25799952
DOI: 10.1016/j.canlet.2015.03.022