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Cellular and Molecular Life Sciences :... Jan 2022In the cartilage matrix, complex interactions occur between angiogenic and anti-angiogenic components, growth factors, and environmental stressors to maintain a proper... (Review)
Review
In the cartilage matrix, complex interactions occur between angiogenic and anti-angiogenic components, growth factors, and environmental stressors to maintain a proper cartilage phenotype that allows for effective load bearing and force distribution. However, as seen in both degenerative disease and tissue engineering, cartilage can lose its vascular resistance. This vascularization then leads to matrix breakdown, chondrocyte apoptosis, and ossification. Research has shown that articular cartilage inflammation leads to compromised joint function and decreased clinical potential for regeneration. Unfortunately, few articles comprehensively summarize what we have learned from previous investigations. In this review, we summarize our current understanding of the factors that stabilize chondrocytes to prevent terminal differentiation and applications of these factors to rescue the cartilage phenotype during cartilage engineering and osteoarthritis treatment. Inhibiting vascularization will allow for enhanced phenotypic stability so that we are able to develop more stable implants for cartilage repair and regeneration.
Topics: Aggrecans; Angiogenesis Inhibitors; Angiostatins; Animals; Apoptosis; Cartilage; Chondrocytes; Cytokines; Endostatins; Humans; Inflammation; Low Density Lipoprotein Receptor-Related Protein-1; Mice; Osteoarthritis; Osteogenesis; Regeneration; Serine Proteinase Inhibitors; Stem Cells; Thrombospondins; Tissue Engineering; Tissue Extracts; Troponin I; Vascular Endothelial Growth Factor A
PubMed: 35029764
DOI: 10.1007/s00018-021-04105-0 -
Bioorganicheskaia Khimiia 2014The main physiological function of plasmin is a blood clot fibrinolysis and restore normal blood flow. To date, however, it became apparent that in addition to... (Review)
Review
The main physiological function of plasmin is a blood clot fibrinolysis and restore normal blood flow. To date, however, it became apparent that in addition to thrombolysis plasminogen/plasmin system plays an important physiological and pathological role in the degradation of extracellular matrix, embryogenesis, cell migration, tissue remodeling, wound healing, angiogenesis, inflammation and tumor cells migration. This review focuses on the structural features of plasminogen, the regulation of its activation by physiological plasminogen activators, inhibitors of plasmin and plasminogen activators, the role of the plasminogen binding to fibrin, cellular receptors and extracellular ligands in performing various functions by formed plasmin.
Topics: Amino Acid Sequence; Angiostatins; Extracellular Matrix; Fibrinolysin; Fibrinolysis; Humans; Inflammation; Neoplasms; Neovascularization, Pathologic; Plasminogen; Plasminogen Activators
PubMed: 25895360
DOI: 10.1134/s1068162014060028 -
Pharmacological Research Aug 2020Angiogenesis is a finely co-ordinated, multi-step developmental process of the new vascular structure. Even though angiogenesis is regularly occurring in physiological... (Review)
Review
Angiogenesis is a finely co-ordinated, multi-step developmental process of the new vascular structure. Even though angiogenesis is regularly occurring in physiological events such as embryogenesis, in adults, it is restricted to specific tissue sites where rapid cell-turnover and membrane synthesis occurs. Both excessive and insufficient angiogenesis lead to vascular disorders such as cancer, ocular diseases, diabetic retinopathy, atherosclerosis, intra-uterine growth restriction, ischemic heart disease, stroke etc. Occurrence of altered lipid profile and vascular lipid deposition along with vascular disorders is a hallmark of impaired angiogenesis. Among lipoproteins, lipoprotein(a) needs special attention due to the presence of a multi-kringle protein subunit, apolipoprotein(a) [apo(a)], which is structurally homologous to many naturally occurring anti-angiogenic proteins such as plasminogen and angiostatin. Researchers have constructed different recombinant forms of apo(a) (rhLK68, rhLK8, RHACK2, KV-11, and AU-6) and successfully exploited its potential to inhibit unwanted angiogenesis during tumor metastasis and retinal neovascularization. Similar to naturally occurring anti-angiogenic proteins, apo(a) can directly interfere with angiogenic signaling pathways. Besides this, apo(a) can also exert its anti-angiogenic effect indirectly by inducing endothelial cell apoptosis, by inhibiting endothelial progenitor cell functions or by upregulating nuclear factors in endothelial cells via apo(a)-bound oxPLs. However, the impact of the anti-angiogenic potential of native apo(a) during physiological angiogenesis in embryos and wounded tissues is not yet explored. In this context, we review the studies so far done to demonstrate the anti-angiogenic activity of apo(a) and the recent developments in using apo(a) as a therapeutic agent to treat impaired angiogenesis during vascular disorders, with emphasis on the gaps in the literature.
Topics: Angiogenesis Inhibitors; Animals; Apolipoproteins A; Humans; Neovascularization, Pathologic; Neovascularization, Physiologic
PubMed: 32430285
DOI: 10.1016/j.phrs.2020.104858 -
Clinical & Translational Oncology :... Oct 2016Angiogenesis, the process of blood vessel formation, is necessary for tissue survival in normal and pathologic conditions. Increased angiogenesis in BM niche is... (Review)
Review
Angiogenesis, the process of blood vessel formation, is necessary for tissue survival in normal and pathologic conditions. Increased angiogenesis in BM niche is correlated with leukemia progression and resistance to treatment. Angiogenesis can interfere with disease progression and several angiogenic (such as vascular growth factors) as well as anti-angiogenic factors (i.e. angiostatin) can affect angiogenesis. Furthermore, miRs can affect the angiogenic process by inhibiting angiogenesis or increasing the expression of growth factors. Given the importance of angiogenesis in BM for maintenance of leukemic clones, recognition of angiogenic and anti-angiogenic factors and miRs as well as drug resistance mechanisms of leukemic blasts can improve the therapeutic strategies. We highlight the changes in angiogenic balance within the BM niche in different leukemia types. Moreover, we explored the pathways leading to drug resistance in relation to angiogenesis and attempted to assign interesting candidates for future research.
Topics: Animals; Bone Marrow; Humans; Leukemia; Neovascularization, Pathologic; Signal Transduction
PubMed: 26742939
DOI: 10.1007/s12094-015-1477-6 -
Reumatologia 2018Inflammation has been revealed to be associated with angiogenesis. Granulomatosis with polyangiitis (GPA) and immune complex small vessel vasculitis (ICSVV) are forms of...
OBJECTIVES
Inflammation has been revealed to be associated with angiogenesis. Granulomatosis with polyangiitis (GPA) and immune complex small vessel vasculitis (ICSVV) are forms of systemic vasculitides of different pathogenesis. GPA is a necrotizing granulomatosis and ICSVV is associated with inflammation of postcapillary venules induced by deposits of immune complexes. The aim of the study was to determine serum levels of angiostatin and endostatin, natural angiogenesis inhibitors, in patients with GPA and ICSVV as well as healthy individuals.
MATERIAL AND METHODS
Two groups of patients with GPA (20 patients) and ICSVV (20 patients) as well as 20 controls were investigated. All patients were investigated before initiation of immunosuppressive therapy or administration of corticosteroids. Angiostatin and endostatin levels were assayed with the ELISA method.
RESULTS
Enhanced serum levels of angiostatin and endostatin were found in patients with GPA but not in those suffering from ICSVV. In patients with GPA increased levels of angiogenesis inhibitors correlated with the disease activity. A correlation between angiostatin and endostatin levels was observed in all groups of investigated individuals.
CONCLUSIONS
It is suggested that formation of necrotizing granulation is associated with profound activation of angiogenesis and an increase in serum levels of inhibitors is a phenomenon occurring during blood vessel formation in the granulation tissue. The obtained results confirm involvement of angiogenesis in pathogenesis of at least some forms of vasculitides and suggest the need for continuation of investigations in this field.
PubMed: 30505009
DOI: 10.5114/reum.2018.79498 -
Allergy Jun 2023
Topics: Humans; Angiostatins; Angiomotins; Airway Remodeling; Microfilament Proteins; Intercellular Signaling Peptides and Proteins; Asthma; Inflammation; Biomarkers
PubMed: 36602260
DOI: 10.1111/all.15637 -
Investigative Ophthalmology & Visual... Sep 2016The primate central retina is characterized by an avascular fovea and well-defined perifoveal capillary plexus. Neither blood vessels nor their accompanying astrocytes...
PURPOSE
The primate central retina is characterized by an avascular fovea and well-defined perifoveal capillary plexus. Neither blood vessels nor their accompanying astrocytes enter the fovea during any stage of retinal development; a balance of angiogenic and angiostatic factors probably maintains foveal avascularity throughout life. The aim of this study was to identify potentially angiorepulsive factors involved in the development of the avascular primate retinal fovea.
METHODS
Retinas of newborn, juvenile, and adult Callithrix jacchus and Macaca fascicularis monkeys and control human retinas were studied to determine the localization of angiostatin relative to III β-tubulin, glial fibrillary acidic protein, vascular endothelial growth factor (VEGF), platelet endothelial cell adhesion molecule-1 (PECAM), and the angiostatin receptor αvβ3-integrin in the foveal, macular, and peripheral retina. Expression studies were performed using immunohistochemistry (IHC) on retinal whole-mount and paraffin sections, and Western blotting on frozen material. The complex network of the main retinal cell types was identified by IHC of retinal whole mounts.
RESULTS
In general, lifetime expression of angiostatin was found in all retinas. Colabeling with different markers revealed retinal ganglion cells as the main source of angiostatin expression in the primate retina, whereas PECAM-immunopositive blood capillaries expressed the angiostatin receptor αvβ3-integrin, and capillary-associated astrocytes expressed VEGF.
CONCLUSIONS
This study provides the first evidence of angiostatin expression in the primate retina; the expression of angiostatin in the avascular foveal region and the peripheral retina suggests that angiostatin may play a role in the regulation of retinal vascularization, providing a possible explanation for the development and persistence of an avascular fovea.
Topics: Aged; Angiostatins; Animals; Animals, Newborn; Blotting, Western; Callithrix; Capillaries; Female; Fovea Centralis; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Macaca fascicularis; Male; Middle Aged; Retinal Ganglion Cells; Retinal Vessels
PubMed: 27583825
DOI: 10.1167/iovs.16-19286 -
Stem Cells International 2024Angiogenesis plays a significant role in the human body, from wound healing to tumor progression. "Angiogenic switch" indicates a time-restricted event where the... (Review)
Review
Angiogenesis plays a significant role in the human body, from wound healing to tumor progression. "Angiogenic switch" indicates a time-restricted event where the imbalance between pro- and antiangiogenic factors results in the transition from prevascular hyperplasia to outgrowing vascularized tumor, which eventually leads to the malignant cancer progression. In the last decade, molecular players, i.e., angiogenic biomarkers and underlying molecular pathways involved in tumorigenesis, have been intensely investigated. Disrupting the initiation and halting the progression of angiogenesis by targeting these biomarkers and molecular pathways has been considered as a potential treatment approach for tumor angiogenesis. This review discusses the currently known biomarkers and available antiangiogenic therapies in cancer, i.e., monoclonal antibodies, aptamers, small molecular inhibitors, miRNAs, siRNAs, angiostatin, endostatin, and melatonin analogues, either approved by the U.S. Food and Drug Administration or currently under clinical and preclinical investigations.
PubMed: 38213742
DOI: 10.1155/2024/9077926 -
Clinical Science (London, England :... Aug 2017Angiogenesis contributes to the pathogenesis of many diseases including exudative age-related macular degeneration (AMD). It is normally kept in check by a tightly... (Review)
Review
Angiogenesis contributes to the pathogenesis of many diseases including exudative age-related macular degeneration (AMD). It is normally kept in check by a tightly balanced production of pro- and anti-angiogenic factors. The up-regulation of the pro-angiogenic factor, vascular endothelial growth factor (VEGF), is intimately linked to the pathogenesis of exudative AMD, and its antagonism has been effectively targeted for treatment. However, very little is known about potential changes in expression of anti-angiogenic factors and the role they play in choroidal vascular homeostasis and neovascularization associated with AMD. Here, we will discuss the important role of thrombospondins and pigment epithelium-derived factor, two major endogenous inhibitors of angiogenesis, in retinal and choroidal vascular homeostasis and their potential alterations during AMD and choroidal neovascularization (CNV). We will review the cell autonomous function of these proteins in retinal and choroidal vascular cells. We will also discuss the potential targeting of these molecules and use of their mimetic peptides for therapeutic development for exudative AMD.
Topics: Angiogenesis Inhibitors; Angiostatins; Choroidal Neovascularization; Endostatins; Eye Proteins; Humans; Macular Degeneration; Molecular Targeted Therapy; Nerve Growth Factors; Serpins; Thrombospondins
PubMed: 28679845
DOI: 10.1042/CS20170066 -
American Journal of Translational... 2021Dyslipidemia aggravates kidney injury distal to atherosclerotic renal artery stenosis (ARAS). Besides dyslipidemia, metabolic syndrome (MetS) also involves development...
BACKGROUND
Dyslipidemia aggravates kidney injury distal to atherosclerotic renal artery stenosis (ARAS). Besides dyslipidemia, metabolic syndrome (MetS) also involves development of obesity and insulin-resistance (IR). We hypothesized that concurrent obesity and IR magnify swine stenotic-kidney damage beyond dyslipidemia.
METHODS
Pigs with unilateral RAS were studied after 16 weeks of atherogenic diets without (ARAS) or with (MetS + RAS) development of obesity/IR (n=6 each). Additional pigs on normal diet served as normal or non-dyslipidemic RAS controls (n=6 each). Stenotic-kidney renal blood flow (RBF), glomerular filtration rate (GFR), and microvascular architecture were studied using CT, and oxygenation was studied using blood oxygen level-dependent magnetic-resonance-imaging. We further compared kidney adiposity, oxidative stress, inflammation, apoptosis, fibrosis, and systemic levels of oxidative and inflammatory cytokines.
RESULTS
ARAS and MetS + RAS developed hypertension and dyslipidemia, and MetS + RAS also developed obesity and IR. RBF and GFR were similarly decreased in all post-stenotic pig kidneys compared to normal pig kidneys, yet MetS + RAS aggravated and expanded medullary hypoxia and microvascular loss. RAS and ARAS increased systemic levels of tumor necrosis factor (TNF)-α, which were further elevated in MetS + RAS. Renal oxidative stress and TNF-α expression increased in ARAS and further in MetS + RAS, which also upregulated expression of anti-angiogenic angiostatin, and magnified apoptosis, tubular injury, and fibrosis.
CONCLUSION
Beyond dyslipidemia, obesity and insulin-resistance aggravate damage in the post-stenotic kidney in MetS, despite relative hyperfiltration-related preservation of renal function. These observations underscore the need to control systemic metabolic disturbances in order to curb renal damage in subjects with ischemic kidney disease.
PubMed: 34540008
DOI: No ID Found