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Bioscience Reports Jan 2021Ghrelin, a 28-aminoacid peptide, was isolated from the human and rat stomach and identified in 1999 as an endogenous ligand for the growth hormone secretagogue-receptor... (Review)
Review
Ghrelin, a 28-aminoacid peptide, was isolated from the human and rat stomach and identified in 1999 as an endogenous ligand for the growth hormone secretagogue-receptor (GHS-R). In addition to stimulating appetite and regulating energy balance, ghrelin and its receptor GHS-R1a have a direct effect on the cardiovascular system. In recent years, it has been shown that ghrelin exerts cardioprotective effects, including the modulation of sympathetic activity and hypertension, enhancement of the vascular activity and angiogenesis, inhibition of arrhythmias, reduction in heart failure and inhibition of cardiac remodeling after myocardial infarction (MI). The cardiovascular protective effect of ghrelin may be associated with anti-inflammation, anti-apoptosis, inhibited sympathetic nerve activation, regulated autophagy, and endothelial dysfunction. However, the molecular mechanisms underlying the effects of ghrelin on the cardiovascular system have not been fully elucidated, and no specific therapeutic agent has been established. It is important to further explore the pharmacological potential of ghrelin pathway modulation for the treatment of cardiovascular diseases.
Topics: Arrhythmias, Cardiac; Blood Vessels; Cardiovascular Diseases; Ghrelin; Humans; Myocardium; Neovascularization, Physiologic
PubMed: 33427286
DOI: 10.1042/BSR20203387 -
Trends in Endocrinology and Metabolism:... Aug 2020Angiogenesis is crucial for the development of the blood vasculature during embryogenesis, but also contributes to cancer and other diseases. While therapeutic targeting... (Review)
Review
Angiogenesis is crucial for the development of the blood vasculature during embryogenesis, but also contributes to cancer and other diseases. While therapeutic targeting of endothelial cells (ECs) through growth factor inhibition is limited by insufficient efficacy and resistance, a new paradigm for modulating angiogenesis by targeting EC metabolism has emerged. Findings from the past decade highlight how ECs adapt their metabolism to proliferate or migrate during vessel sprouting, or to maintain the vascular barrier and protect themselves against oxidative stress in the high-oxygen environment they are exposed to in healthy conditions. We overview key endothelial metabolic pathways underlying the different EC phenotypes, as well as potential opportunities for targeting EC metabolism in therapeutic settings.
Topics: Animals; Endothelial Cells; Humans; Neovascularization, Pathologic; Neovascularization, Physiologic; Oxidative Stress
PubMed: 32622584
DOI: 10.1016/j.tem.2020.05.009 -
Lung Cancer (Amsterdam, Netherlands) Aug 2023The chemotherapy drugs for NSCLC often face the consequences of treatment failure due to acquired drug resistance. Tumor chemotherapy resistance is often accompanied by...
AIMS
The chemotherapy drugs for NSCLC often face the consequences of treatment failure due to acquired drug resistance. Tumor chemotherapy resistance is often accompanied by angiogenesis. Here, we aimed to investigate the effect and underlying mechanisms of ADAM-17 inhibitor ZLDI-8 we found before on angiogenesis and vasculogenic mimicry(VM) in drug-resistant NSCLC.
MAIN METHODS
The tube formation assay was used to evaluate angiogenesis and VM. Migration and invasion were assessed with transwell assays in the co-culture condition. To explore the underlying mechanisms of how ZLDI-8 inhibited tubes formation, ELISA assay and western blot assay were preformed. The effects of ZLDI-8 on angiogenesis in vivo were investigated in Matrigel plug, CAM and Rat aortic ring assays.
KEY FINDINGS
In the present study, ZLDI-8 significantly inhibited the tube formation of human umbilical vein endothelial cells (HUVECs) in either normal medium or in tumor supernatants. Furthermore, ZLDI-8 also inhibited VM tubes formation of A549/Taxol cells. In the co-culture assay, the interaction between lung cancer cells and HUVECs promotes increased cell migration and invasion, while ZLDI-8 eliminates this promotion. Moreover, the VEGF secretion were decreased by ZLDI-8 and the expression of Notch1, Dll4, HIF1α and VEGF were inhibited by ZLDI-8. In addition, ZLDI-8 can inhibit blood vessel formation in the Matrigel plug, CAM and Rat aortic ring assays.
SIGNIFICANCE
ZLDI-8 inhibits angiogenesis and VM in drug-resistant NSCLC through suppressing Notch1-HIF1α-VEGF signaling pathway. This study lays the foundation for the discovery of drugs that inhibit angiogenesis and VM in drug resistant NSCLC.
Topics: Humans; Rats; Animals; Lung Neoplasms; Endothelial Cells; Vascular Endothelial Growth Factor A; Cell Line, Tumor; Neovascularization, Pathologic; Carcinoma, Non-Small-Cell Lung; Cell Movement; Human Umbilical Vein Endothelial Cells
PubMed: 37364397
DOI: 10.1016/j.lungcan.2023.107279 -
Cells Dec 2021Exposure to the antibacterial agent triclosan (TCS) is associated with abnormal placenta growth and fetal development during pregnancy. Peroxisome proliferator-activated...
Exposure to the antibacterial agent triclosan (TCS) is associated with abnormal placenta growth and fetal development during pregnancy. Peroxisome proliferator-activated receptor γ (PPARγ) is crucial in placenta development. However, the mechanism of PPARγ in placenta injury induced by TCS remains unknown. Herein, we demonstrated that PPARγ worked as a protector against TCS-induced toxicity. TCS inhibited cell viability, migration, and angiogenesis dose-dependently in HTR-8/SVneo and JEG-3 cells. Furthermore, TCS downregulated expression of PPARγ and its downstream viability, migration, angiogenesis-related genes , , , , , and upregulated inflammatory genes , , , and in vitro and in vivo. Further investigation showed that overexpression or activation (rosiglitazone) alleviated cell viability, migration, angiogenesis inhibition, and inflammatory response caused by TCS, while knockdown or inhibition (GW9662) of PPARγ had the opposite effect. Moreover, TCS caused placenta dysfunction characterized by the significant decrease in weight and size of the placenta and fetus, while PPARγ agonist rosiglitazone alleviated this damage in mice. Taken together, our results illustrated that TCS-induced placenta dysfunction, which was mediated by the PPARγ pathway. Our findings reveal that activation of PPARγ might be a promising strategy against the adverse effects of TCS exposure on the placenta and fetus.
Topics: Animals; Cell Line; Cell Movement; Cell Survival; Female; Gene Expression Regulation; Humans; Inflammation; Mice; Models, Biological; Neovascularization, Physiologic; PPAR gamma; Placenta; Pregnancy; Triclosan
PubMed: 35011648
DOI: 10.3390/cells11010086 -
Cells Aug 2020Previously, we demonstrated that the homeoprotein Msx1 interaction with p53 inhibited tumor growth by inducing apoptosis. However, Msx1 can exert its tumor suppressive...
Previously, we demonstrated that the homeoprotein Msx1 interaction with p53 inhibited tumor growth by inducing apoptosis. However, Msx1 can exert its tumor suppressive effect through the inhibition of angiogenesis since growth of the tumor relies on sufficient blood supply from the existing vessels to provide oxygen and nutrients for tumor growth. We hypothesized that the inhibition of tumor growth by Msx1 might be due to the inhibition of angiogenesis. Here, we explored the role of Msx1 in angiogenesis. Overexpression of Msx1 in HUVECs inhibited angiogenesis, and silencing of Msx1 by siRNA abrogated its anti-angiogenic effects. Furthermore, forced expression of Msx1 in mouse muscle tissue inhibited vessel sprouting, and application of an Ad-Msx1-transfected conditioned medium onto the chicken chorioallantoic membrane (CAM) led to a significant inhibition of new vessel formation. To explore the underlying mechanism of Msx1-mediated angiogenesis, yeast two-hybrid screening was performed, and we identified PIASy (protein inhibitor of activated STAT Y) as a novel Msx1-interacting protein. We mapped the homeodomain of Msx1 and the C-terminal domain of PIASy as respective interacting domains. Consistent with its anti-angiogenic function, overexpression of Msx1 suppressed the reporter activity of VEGF. Interestingly, PIASy stabilized Msx1 protein, whereas deletion of the Msx1-interacting domain in PIASy abrogated the inhibition of tube formation and the stabilization of Msx1 protein. Our findings suggest the functional importance of PIASy-Msx1 interaction in Msx1-mediated angiogenesis inhibition.
Topics: Animals; Chick Embryo; Human Umbilical Vein Endothelial Cells; Humans; MSX1 Transcription Factor; Mice; Mice, Inbred BALB C; Neovascularization, Physiologic; Poly-ADP-Ribose Binding Proteins; Protein Binding; Protein Inhibitors of Activated STAT; Vascular Endothelial Growth Factor A
PubMed: 32784646
DOI: 10.3390/cells9081854 -
Current Rheumatology Reviews 2021Endostatin by its therapeutic value against rheumatoid arthritis has recently gained significant interest in biomedical science. A recent study revealed that various... (Review)
Review
BACKGROUND
Endostatin by its therapeutic value against rheumatoid arthritis has recently gained significant interest in biomedical science. A recent study revealed that various approaches have been made to prevent rheumatoid arthritis by either controlling or inhibiting the progression of angiogenesis.
OBJECTIVE
The main objective of the current manuscript is to enumerate the intrinsic role of endostatin in rheumatoid arthritis.
METHODS
A thorough and detailed review of literature from the papers published from the year 1997-2019 was studied for the preparation of the current article.
RESULTS
Endostatin is one such agent of the subfamily of ECM called as multiplexins obtained from proteolytic cleavage of XVIII and its carboxylic terminal fragments and is known for its antiangiogenic and antiproliferative property. The exact mechanism of endostatin is still unclear, but it acts by downregulating or inhibiting the responses of various factors, including Id1, Id3, matrix metalloproteinase, and Nuclear factor Kappa B that are liable for angiogenesis. The mutual effects on adipogenesis and angiogenesis, endostatin inhibits dietary-induced obesity and its related metabolic disorders, such as insulin resistance, glucose intolerance, and hepatic steatosis.
CONCLUSION
The present review demonstrates the intrinsic usage of endostatin as a novel molecule in rheumatoid arthritis. It focuses on the status of the therapeutic potential of endostatin in inhibiting the activity of angiogenesis is also very well explored.
Topics: Arthritis, Rheumatoid; Endostatins; Humans; Neovascularization, Pathologic
PubMed: 32348230
DOI: 10.2174/1573397115666191127141801 -
Experimental Eye Research Sep 2023Proliferative diabetic retinopathy (PDR) adversely affects visual function. Extracellular matrix proteins (ECM) contribute significantly to the development of PDR. A...
Proliferative diabetic retinopathy (PDR) adversely affects visual function. Extracellular matrix proteins (ECM) contribute significantly to the development of PDR. A Disintegrin and Metalloproteinase with Thrombospondin motifs 5 (ADAMTS5) is a member of ECM proteins. ADAMTS5 participates in angiogenesis and inflammation in diverse diseases. However, the role of ADAMTS5 in PDR remains elusive. Multiplex beam array technology was used to analyze vitreous humor of PDR patients and normal people. ELISA and Western blot were used to detect the expression of ADAMTS5, PEDF and autophagy related factors. Immunofluorescence assay was used to mark the expression and localization of ADAMTS5 and PEDF. The neovascularization was detected by tube formation test. Our results revealed that ADAMTS5 expression was increased in the vitreous humor of PDR patients and oxygen-induced retinopathy (OIR) mice retinas. Inhibiting ADAMTS5 alleviated pathological angiogenesis and upregulated PEDF expression in the OIR mice. In addition, ADAMTS5 inhibited PEDF secretion in ARPE-19 cells in vitro studies, thereby inhibiting the migration of HMEC-1. Mechanically, ADAMTS5 promoted the autophagic degradation of PEDF. Collectively, inhibition of ADAMTS5 during OIR suppresses pathological angiogenesis. Our study provides a new approach for resolving pathological angiogenesis in PDR.
Topics: Animals; Mice; Autophagy; Diabetes Mellitus; Diabetic Retinopathy; Eye Proteins; Neovascularization, Pathologic; Retinal Diseases; Retinal Neovascularization; Serpins
PubMed: 37490993
DOI: 10.1016/j.exer.2023.109597 -
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 -
Medicina (Kaunas, Lithuania) Jul 2022Angiogenesis is the process of developing new blood vessels from pre-existing ones. This review summarizes the main features of physiological and pathological... (Review)
Review
Angiogenesis is the process of developing new blood vessels from pre-existing ones. This review summarizes the main features of physiological and pathological angiogenesis and those of angiogenesis activation and inhibition. In healthy adults, angiogenesis is absent apart from its involvement in female reproductive functions and tissue regeneration. Angiogenesis is a complex process regulated by the action of specific activators and inhibitors. In certain diseases, modulating the angiogenic balance can be a therapeutic route, either by inhibiting angiogenesis (for example in the case of tumor angiogenesis), or by trying to activate the process of new blood vessels formation, which is the goal in case of cardiac or peripheral ischemia.
Topics: Angiogenesis Inhibitors; Cardiovascular Diseases; Female; Humans; Neoplasms; Neovascularization, Pathologic
PubMed: 35888622
DOI: 10.3390/medicina58070903 -
International Journal of Molecular... May 2021Retinopathy of prematurity (ROP) is an ocular vascular disease affecting premature infants, characterized by pathological retinal neovascularization (RNV), dilated and... (Review)
Review
Retinopathy of prematurity (ROP) is an ocular vascular disease affecting premature infants, characterized by pathological retinal neovascularization (RNV), dilated and tortuous retinal blood vessels, and retinal or vitreous hemorrhages that may lead to retinal detachment, vision impairment and blindness. Compared with other neovascular diseases, ROP is unique because of ongoing and concurrent physiological and pathological angiogenesis in the developing retina. While the disease is currently treated by laser or cryotherapy, anti-vascular endothelial growth factor (VEGF) agents have been extensively investigated but are not approved in the U.S. because of safety concerns that they negatively interfere with physiological angiogenesis of the developing retina. An ideal therapeutic strategy would selectively inhibit pathological but not physiological angiogenesis. Our group recently described a novel strategy that selectively and safely alleviates pathological RNV in animal models of ROP by targeting secretogranin III (Scg3), a disease-restricted angiogenic factor. The preclinical profile of anti-Scg3 therapy presents a high potential for next-generation disease-targeted anti-angiogenic therapy for the ROP indication. This review focuses on retinal vessel development in neonates, the pathogenesis of ROP and its underlying molecular mechanisms, including different animal models, and provides a summary of current and emerging therapies.
Topics: Animals; Animals, Newborn; Chromogranins; Humans; Mice; Neovascularization, Pathologic; Neovascularization, Physiologic; Oxygen; Retina; Retinopathy of Prematurity; Vascular Endothelial Growth Factor A
PubMed: 34062733
DOI: 10.3390/ijms22094809