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Immune Network Dec 2021Recently, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (B.1.1.529) Omicron variant originated from South Africa in the middle of November 2021.... (Review)
Review
Recently, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (B.1.1.529) Omicron variant originated from South Africa in the middle of November 2021. SARS-CoV-2 is also called coronavirus disease 2019 (COVID-19) since SARS-CoV-2 is the causative agent of COVID-19. Several studies already suggested that the SARS-CoV-2 Omicron variant would be the fastest transmissible variant compared to the previous 10 SARS-CoV-2 variants of concern, interest, and alert. Few clinical studies reported the high transmissibility of the Omicron variant but there is insufficient time to perform actual experiments to prove it, since the spread is so fast. We analyzed the SARS-CoV-2 Omicron variant, which revealed a very high rate of mutation at amino acid residues that interact with angiostatin-converting enzyme 2. The mutation rate of COVID-19 is faster than what we prepared vaccine program, antibody therapy, lockdown, and quarantine against COVID-19 so far. Thus, it is necessary to find better strategies to overcome the current crisis of COVID-19 pandemic.
PubMed: 35036025
DOI: 10.4110/in.2021.21.e38 -
Journal of Visualized Experiments : JoVE Mar 2021Lungs are continually faced with direct and indirect insults in the form of sterile (particles or reactive toxins) and infectious (bacterial, viral or fungal)...
Lungs are continually faced with direct and indirect insults in the form of sterile (particles or reactive toxins) and infectious (bacterial, viral or fungal) inflammatory conditions. An overwhelming host response may result in compromised respiration and acute lung injury, which is characterized by lung neutrophil recruitment as a result of the patho-logical host immune, coagulative and tissue remodeling response. Sensitive microscopic methods to visualize and quantify murine lung cellular adaptations, in response to low-dose (0.05 ppm) ozone, a potent environmental pollutant in combination with bacterial lipopolysaccharide, a TLR4 agonist, are crucial in order to understand the host inflammatory and repair mechanisms. We describe a comprehensive fluorescent microscopic analysis of various lung and systemic body compartments, namely the broncho-alveolar lavage fluid, lung vascular perfusate, left lung cryosections, and sternal bone marrow perfusate. We show damage of alveolar macrophages, neutrophils, lung parenchymal tissue, as well as bone marrow cells in correlation with a delayed (up to 36-72 h) immune response that is marked by discrete chemokine gradients in the analyzed compartments. In addition, we present lung extracellular matrix and cellular cytoskeletal interactions (actin, tubulin), mitochondrial and reactive oxygen species, anti-coagulative plasminogen, its anti-angiogenic peptide fragment angiostatin, the mitochondrial ATP synthase complex V subunits, α and β. These surrogate markers, when supplemented with adequate in vitro cell-based assays and in vivo animal imaging techniques such as intravital microscopy, can provide vital information towards understanding the lung response to novel immunomodulatory agents.
Topics: Acute Lung Injury; Animals; Disease Models, Animal; Lipopolysaccharides; Mice; Neutrophil Infiltration; Ozone
PubMed: 33818567
DOI: 10.3791/62097 -
Lupus Oct 2014We found, in 1994, that the epitope for anticardiolipin antibodies (aCL) developed when β2-glycoprotein I (β2GPI) was adsorbed on polyoxygenated polystyrene plates. We...
We found, in 1994, that the epitope for anticardiolipin antibodies (aCL) developed when β2-glycoprotein I (β2GPI) was adsorbed on polyoxygenated polystyrene plates. We also found, in 2009, that the cleaved form of β2GPI (nicked β2GPI) was bound to angiostatin 4.5 and attenuated its antiangiogenic property. We described in 2000 that antiprothrombin antibodies were bound to prothrombin exposed to immobilized phosphatidylserine (aPS/PT) and more than 95% of antiphospholipid syndrome patients who were positive for aPS/PT had lupus anticoagulant. We demonstrated that in the cells stimulated by human monoclonal anti-β2GPI antibodies, p38 mitogen-activated protein kinase phosphorylation was observed in the presence of β2GPI. Furthermore, we found that complement activation was essential for thrombus formation in patients with the antiphospholipid syndrome in vivo.
Topics: Antibodies, Anticardiolipin; Antiphospholipid Syndrome; Complement Activation; Complement C5; Genetic Predisposition to Disease; Humans; Prothrombin; Thrombosis; beta 2-Glycoprotein I
PubMed: 25228741
DOI: 10.1177/0961203314534306 -
Life Sciences Aug 2015Angiogenesis and chronic inflammation are known to be co-dependent in atherosclerosis and cardiovascular diseases. This study was undertaken to investigate whether... (Clinical Trial)
Clinical Trial
AIM
Angiogenesis and chronic inflammation are known to be co-dependent in atherosclerosis and cardiovascular diseases. This study was undertaken to investigate whether simvastatin could affect serum levels of angiostatin, a potent endogenous inhibitor of neovascularization, in patients with ischemic heart disease (IHD).
MAIN METHODS
Twenty-six patients with clinically confirmed IHD and hypercholesterolemia were assigned 40 mg/day of simvastatin for 8 weeks. Levels of lipid metabolism, C-reactive protein (C-RP) and other biochemical parameters in serum samples were measured using biochemical analyzer. Serum angiostatin levels were determined by Western blot. Association of serum angiostatin levels with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and C-RP levels was evaluated.
KEY FINDINGS
Simvastatin therapy improved the main parameters of lipid metabolism, including statistically significant (P < 0.05) reductions in TC (by 46%) and LDL-C (by 42%), and decreased inflammatory marker C-RP (by 32%), as compared with the baseline. Simvastatin treatment resulted in marked reduction of serum angiostatin level (by 80% in comparison with baseline, P < 0.05). Strong positive correlations between serum angiostatin level versus concentrations of TC, LDL-C, and C-RP were demonstrated before onset of the study (r = 0.48311, 0.6252, and 0.653, respectively) and after simvastatin therapy (r = 0.67752, 0.6485, and 0.8244, respectively).
SIGNIFICANCE
We describe for the first time novel pleiotropic effect of statin therapy associated with decrease of serum angiostatin levels. Thus, circulating angiostatin represents an independent additional risk marker for cardiovascular events and could be applied as potential supplementary indicator for evaluation of statin therapy efficacy.
Topics: Aged; Angiostatins; C-Reactive Protein; Cholesterol, LDL; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Myocardial Ischemia
PubMed: 26032258
DOI: 10.1016/j.lfs.2015.05.008 -
The Journal of Surgical Research Feb 2015Epidemiologic studies have demonstrated that daily low to moderate alcohol consumption is cardioprotective as compared with abstainers and high alcohol consumption. Our...
BACKGROUND
Epidemiologic studies have demonstrated that daily low to moderate alcohol consumption is cardioprotective as compared with abstainers and high alcohol consumption. Our group reported that alcohol consumption improves angiogenesis in chronically ischemic myocardium. We developed a clinically relevant follow-up study to assess the effect of moderate alcohol consumption on new vessel growth in normal myocardium remote from an ischemic territory in a swine model.
MATERIALS AND METHODS
Fourteen male Yorkshire swine underwent placement of an ameroid constrictor to induce chronic myocardial ischemia. Postoperatively, animals were supplemented with either 90 mL of ethanol daily (ETOH) or 80 g of sucrose (SUC) of equal caloric value. Seven weeks after ameroid placement, myocardial tissue from a territory remote from the ischemia was harvested for analysis.
RESULTS
Both groups had similar microvascular relaxation to endothelial dependent and endothelium-independent vasodilators. Also, both groups had similar myocardial perfusion at rest and with demand pacing. The ETOH group had significantly increased arteriolar and capillary density in the nonischemic myocardium compared with the SUC group. ETOH supplementation also increased expression of pro-angiogenesis proteins vascular endothelial growth factor and vascular endothelial cadherin, and decreased expression of anti-angiogenesis proteins angiostatin and endostatin.
CONCLUSIONS
ETOH supplementation increased capillary and arteriolar density, upregulated pro-angiogenesis and pro-survival proteins, and downregulated anti-angiogenesis protein expression. These findings suggest that at moderate doses, ETOH directly promotes new vessel growth in the nonischemic myocardium remote from chronic ischemia.
Topics: Alcohol Drinking; Angiogenic Proteins; Animals; Central Nervous System Depressants; Disease Models, Animal; Endothelium, Vascular; Ethanol; Male; Microvessels; Myocardial Ischemia; Myocardial Perfusion Imaging; Neovascularization, Physiologic; Swine; Vasodilation
PubMed: 24961889
DOI: 10.1016/j.jss.2014.05.048 -
Journal of Oncology 2020The aim of the study is to investigate the expression of angiogenesis (VEGF and PDGF), angiogenesis inhibitor markers (angiostatin and endostatin), proliferation (Ki67),...
The aim of the study is to investigate the expression of angiogenesis (VEGF and PDGF), angiogenesis inhibitor markers (angiostatin and endostatin), proliferation (Ki67), and apoptosis markers (p53 and p16) of cervical cancer in Indian population and to correlate them with the clinicopathological profile. It is a descriptive study of consecutive cases of cervical cancer from Saveetha Medical College and Hospital between January 2017 and December 2018. The expression of angiogenesis, angiogenesis inhibitor markers, Ki67, p53, and p16 in 60 cases of cervical sections were detected by the immunohistochemical method and analyzed with clinicopathological data. VEGF expression was positive in 16 cases (26.67%) and negative in 20 cases (33.33%). As of PDGF, 3 cases (3.33%) have shown positivity to PDGF and 33 cases have shown negativity. Angiostatin and endostatin expression was reported to be positive in 10 (16.67%) and 21 (35%) cases, respectively. Most of the cases 57 (95%) have shown both p16 and Ki67 positivity. Although p53 expression was positive in 48 cases (80%), the remaining 12 cases (20%) were p53-negative. The PDGF expression was significantly correlated to the stage of tumors. No statistically significant association was observed between angiogenesis inhibitor markers and clinicopathological parameters. A significant positive correlation was noticed between the Ki67 expression and stage of tumors.
PubMed: 33273920
DOI: 10.1155/2020/8541415 -
Cellular and Molecular Biology... Feb 2022Gallbladder cancer is one of the gastrointestinal tumors with an extremely poor prognosis. Its incidence rate is gradually increasing worldwide, and the rate of radical...
Gallbladder cancer is one of the gastrointestinal tumors with an extremely poor prognosis. Its incidence rate is gradually increasing worldwide, and the rate of radical resection surgery is extremely low. Not sensitive to radiotherapy and chemotherapy, with a very poor prognosis. This study aimed to investigate whether the recombinant mouse angiostatin gene transfected anti-angiogenic gallbladder cancer cells can express angiostatin protein with the activity of inhibiting the growth of vascular endothelial cells and the inhibitory effect on the growth of gallbladder cancer. The recombinant mouse angiostatin gene eukaryotic expression plasmid was transfected into the gallbladder cancer cell line by applying liposome LIPOFECTAMINE 2000, and its activity was detected by vascular endothelial cell proliferation analysis. The results show that angiostatin can inhibit the growth of transplanted gallbladder cancer, and as the number of injections increases, the inhibition rate of gallbladder cancer growth also increases. At the end of the experiment, the total inhibition rate of gallbladder cancer growth reached 95% 5%, 20%, 30%, 40% gradually increase. Therefore, angiostatin has potential clinical application value in gene therapy of gallbladder cancer.
Topics: Angiostatins; Animals; Cell Proliferation; Endothelial Cells; Gallbladder Neoplasms; Genetic Therapy; Mice; Peptide Fragments
PubMed: 35818206
DOI: 10.14715/cmb/2021.67.6.16 -
Pathology, Research and Practice Nov 2023Oxysterols and oxysterol-metabolizing enzymes have been implicated in the pathogenesis of various cancers. However, the distinct function of the oxysterol-metabolizing...
Oxysterols and oxysterol-metabolizing enzymes have been implicated in the pathogenesis of various cancers. However, the distinct function of the oxysterol-metabolizing enzyme cytochrome P450 family 39 Subfamily A Member 1 (CYP39A1) in colorectal cancer (CRC) remains unclear. The aims of the current study were to evaluate whether CYP39A1 affects the oncogenic behaviors of CRC cells and to investigate the prognostic value of its expression in CRC. A CYP39A1 small-interfering RNA was used to block CYP39A1 gene expression in DLD1 and SW480 cells. The expression of CYP39A1 in CRC tissues was investigated by immunohistochemistry. Tumor angiogenesis and lymphangiogenesis were assessed by CD34 and D2-40 immunohistochemical staining, respectively. CYP39A1 knockdown inhibited tumor cell migration and invasion in DLD1 and SW480 cells. Angiogenesis was also inhibited through the decreased expression of vascular endothelial growth factor (VEGF)-A and hypoxia-inducible factor (HIF)-1α, and angiostatin and endostatin expression increased. In addition, CYP39A1 knockdown inhibited the lymphangiogenesis by decreasing the expression of VEGF-C. CYP39A1 expression was increased in CRC tissues compared with normal colorectal mucosa. CYP39A1 expression was associated with tumor stage, depth of invasion, lymph node metastasis, distant metastasis, and poor survival. The microvessel and lymphatic vessel density values of CYP39A1-positive tumors were significantly higher than those of CYP39A1-negative tumors. These results indicate that CYP39A1 is associated with tumor progression by influencing tumor cell angiogenesis and lymphangiogenesis in CRC.
Topics: Humans; Vascular Endothelial Growth Factor A; Oxysterols; Prognosis; Lymphatic Vessels; Lymphangiogenesis; Colorectal Neoplasms; Steroid Hydroxylases
PubMed: 37820439
DOI: 10.1016/j.prp.2023.154875 -
Cell Transplantation Nov 2018Osteoarthritis (OA) is degenerative disease, leading to pain and functional disability. It is reported that polydeoxyribonucleotide (PDRN) is a suitable therapy for OA....
Osteoarthritis (OA) is degenerative disease, leading to pain and functional disability. It is reported that polydeoxyribonucleotide (PDRN) is a suitable therapy for OA. However, the therapeutic mechanisms of PDRN in OA are not fully understood. To investigate the effect of PDRN in an model of OA, interleukin (IL)-1β or phosphate-buffered saline (PBS) was used to treat a human chondrocytic cell line in hypoxic conditions for 24 h (IL-1β group or control group). PDRN was then used to treat IL-1β group cells for 24 h (PDRN group). By Label-Based Human Antibody Array 1000, angiopoietin-2 (ANG-2), platelet-derived growth factor (PDGF), angiostatin, and endostatin, which were related to angiogenesis, were chosen for further validation studies. Quantitative real-time reverse transcription polymerase chain reaction and western blot analysis validated that the levels of PDGF and ANG-2, which were related to pro-angiogenesis, were significantly increased in the PDRN group compared with those in the control group or the IL-1β group. However, the levels of endostatin and angiostatin, which were related in anti-angiogenesis, were significantly decreased in the PDRN group compared with those in the control group or the IL-1β group. In the same manner, vascular endothelial growth factor, which was a mediator of angiogenesis, was significantly increased in the PDRN group compared with those in the control group or the IL-1β group. Furthermore, wound closure was significantly increased in the PDRN group compared with the control group or the IL-1β group by scratch assay. Moreover, PDRN decreased expression of metalloproteinase 13, as a catabolic factor for OA, but increased expression of aggrecan, which was an anabolic factor for OA. These data suggest that PDRN may promote angiogenesis and wound healing via down-regulation of catabolism and up-regulation of anabolism in an model of OA.
PubMed: 30311500
DOI: 10.1177/0963689718804130 -
Frontiers in Cardiovascular Medicine 2024Fabry's disease is an X-linked lysosomal storage disorder caused by reduced activity of α-galactosidase A (GAL), leading to premature death on account of renal,...
Overexpression of VEGFα as a biomarker of endothelial dysfunction in aortic tissue of α-GAL-Tg/KO mice and its upregulation in the serum of patients with Fabry's disease.
INTRODUCTION
Fabry's disease is an X-linked lysosomal storage disorder caused by reduced activity of α-galactosidase A (GAL), leading to premature death on account of renal, cardiac, and vascular organ failure. Accumulation of the GAL substrate globotriaosylceramide (Gb3) in endothelial and smooth muscle cells is associated with early vascular cell damage, suggesting endothelial dysfunction as a driver of cardiorenal organ failure. Here, we studied the vascular expression of the key angiogenic factors, VEGFα and its antagonist angiostatin, in Fabry α-GAL-Tg/KO mice and determined circulating VEGFα and angiostatin serum levels in patients with Fabry's disease and healthy controls.
METHODS
Cryopreserved aortic vessels from six α-GAL-Tg/KO and six wild-type (WT) mice were obtained and VEGFα and angiostatin levels were determined by performing Western blot analysis. VEGFα expression was visualized by an immunohistochemical staining of paraffin aortic rings. In addition, VEGFα and angiostatin serum levels were measured by using an enzyme-linked immunosorbent assay in 48 patients with genetically verified Fabry's disease (50% male) and 22 healthy controls and correlated with disease severity markers such as lyso-Gb3, albuminuria, NTproBNP, high-sensitive troponin T (hsTNT), and myocardial wall thickness.
RESULTS
It was found that there was a significant increase in VEGFα protein expression (1.66 ± 0.35 vs. 0.62 ± 0.16, = 0.0009) and a decrease in angiostatin expression (0.024 ± 0.007 vs. 0.053 ± 0.02, = 0.038) in aortic lysates from α-GAL-Tg/KO compared with that from WT mice. Immunohistochemical staining revealed an adventitial VEGFα signal in α-GAL-Tg/KO mice, whereas no VEGFα signal could be detected in WT mice aortas. No differences in aortic angiostatin expression between α-GAL-Tg/KO- and WT mice could be visualized. The serum levels of VEGFα were significantly upregulated in patients with Fabry's disease compared with that in healthy controls (708.5 ± 426.3 vs. 458.5 ± 181.5 pg/ml, = 0.048) and positively associated with albuminuria ( = 0.82, < 0.0001) and elevated NTproBNP ( = 0.87, < 0.0001) and hsTNT values ( = 0.41, = 0.048) in male patients with Fabry's disease. For angiostatin, no significant difference was found between patients with Fabry's disease and healthy controls (747.6 ± 390.3 vs. 858.8 ± 599.3 pg/ml).
DISCUSSION
In conclusion, an overexpression of VEGFα and downregulation of its counter player angiostatin in aortic tissue of α-GAL-Tg/KO mice support the hypothesis of an underlying vasculopathy in Fabry's disease. Elevated VEGFα serum levels were also observed in patients with Fabry's disease and were positively associated with elevated markers of organ manifestation in males. These findings suggest that angiogenetic markers, such as VEGFα, may be potentially useful biomarkers for the detection of endothelial dysfunction in classical Fabry's disease.
PubMed: 38374995
DOI: 10.3389/fcvm.2024.1355033