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Nutrients Jun 2021The aim of our study was to evaluate if endothelial-dysfunction (ED) occurs in patients with primary Sjogren syndrome (pSS) and whether it is associated with the disease...
The aim of our study was to evaluate if endothelial-dysfunction (ED) occurs in patients with primary Sjogren syndrome (pSS) and whether it is associated with the disease characteristics and activity. A total of 46 patients with pSS and 30 controls, without known cardiovascular disease, were enrolled in this study. A flow-mediated-dilation (FMD) of the brachial artery, plasma concentrations of the nitric oxide (NO) metabolic pathway (ADMA, L-arginine, SDMA, cGMP), and markers of endothelial inflammatory function (PAI-1, sE-selectin) and angiogenesis (angiostatin, VEGF) were analyzed. The FMD was significantly lower in pSS patients (7.56 ± 3.08 vs. 10.91 ± 1.02%, = 0.043) and positively correlated with the Ro/SS-A-antibodies ( = 0.34, = 0.03), pulmonary involvement ( = 0.52, = 0.001) and inversely with ADMA ( = -0.35, = 0.04). Plasma ADMA, L-arginine and angiostatin levels were significantly higher in pSS patients (0.39 ± 0.08 vs. 0.36 ± 0.06 µmol/L, = 0.05; 29.07 ± 6.7 vs. 25.4 ± 5.23 µmol/L, = 0.01; 152.25 ± 60.99 vs. 120.07 ± 38.7 pg/mL, = 0.0, respectively). ADMA was associated with ESSDAI ( = 0.33, = 0.02), SCORE ( = 0.57, = 0.00003) and focus score ( = 0.38, = 0.04). In the multiple regression analysis, the ESSDAI was significantly and independently associated with plasma ADMA levels ( = 0.24, = 0.04). Moreover, plasma cGMP concentrations were negatively correlated with the disease duration ( = -0.31, = 0.03). Endothelial function is impaired in patients with pSS and associated with the measures of disease activity, which supports the key-role of inflammation in developing and maintaining accelerated atherosclerosis.
Topics: Adult; Arginine; Biomarkers; Brachial Artery; Cardiovascular Diseases; Endothelium, Vascular; Female; Heart Disease Risk Factors; Humans; Inflammation; Male; Middle Aged; Regression Analysis; Sjogren's Syndrome; Vascular Diseases
PubMed: 34204342
DOI: 10.3390/nu13062072 -
Angiogenesis Feb 2018Intracranial atherosclerotic disease (ICAD) is one of the most common causes of stroke worldwide and the one with the worst prognosis. In this study, we assessed the... (Clinical Trial)
Clinical Trial Observational Study
Intracranial atherosclerotic disease (ICAD) is one of the most common causes of stroke worldwide and the one with the worst prognosis. In this study, we assessed the hypothesis that the balance of circulating pro- and antiangiogenic factors plays a role in the evolution of the disease and can be used as a potential marker for the disease course and a target for treatment. Seventy-four patients with severe ICAD were enrolled in this prospective observational study, medically optimized, and followed for 6 months. Thirteen pro- and eight antiangiogenic factors were measured in the participants' serum using a sandwich multiplex ELISA. Angiogenic profiles were calculated using principal component analysis. We tested the association between angiogenic profiles and recurring cerebrovascular events despite intensive medical therapy, disability at 6 months after enrollment, and angiographic neovascularization in patients who failed medical treatment and underwent indirect revascularization surgery. There is a strong association between a functionally antiangiogenic profile and recurrent stroke or TIA in patients with ICAD (OR = 7.2, CI 2.4-34.4). Multivariable regression analysis showed that this antiangiogenic profile was also associated with poor functional status after 6 months (p = 0.002), independent from other clinical features such as history of previous stroke, diabetes, and age. In patients who failed medical management and underwent indirect revascularization surgery, high endostatin and angiostatin levels were also associated with low angiographic neovascularization (p = 0.02). The results of this study point to the striking importance of antiangiogenesis as a determinant of ICAD patient prognosis and suggest a possible new target for therapy.
Topics: Adult; Aged; Aged, 80 and over; Angiostatins; Endostatins; Follow-Up Studies; Humans; Intracranial Arteriosclerosis; Ischemic Attack, Transient; Longitudinal Studies; Middle Aged; Neovascularization, Pathologic; Prognosis; Prospective Studies; Regression Analysis; Stroke
PubMed: 28993906
DOI: 10.1007/s10456-017-9578-1 -
Autoimmunity Reviews Feb 2015Vasculopathy has a major role in the pathogenesis and tissue injury in systemic sclerosis (SSc). Raynaud's phenomenon (RP) is frequently the first clinical manifestation... (Review)
Review
Vasculopathy has a major role in the pathogenesis and tissue injury in systemic sclerosis (SSc). Raynaud's phenomenon (RP) is frequently the first clinical manifestation of SSc preceding by years other clinical manifestations. RP in SSc patients is frequent, often very severe and long lasting. The repeated bouts of RP lead to prolonged digital ischemia that may progress to digital ulceration or in extreme to critical digital ischemia with gangrene. Digital ulcers (DU) are a true burden for all patients. They are very painful, with a long and slow healing course, have high risk of infection and are extremely disabling. In adults, up to 40-50% of patients will experience at least one DU in the course of the disease and of these 31-71% will have recurrent ulcers. In order to try to identify predictive risk factors for DU in SSc patients, an extensive literature review was conducted, according to the guidelines proposed at the PRISMA statement. MEDLINE database (PubMed) and Thomson Reuters Web of Knowledge platform were searched for articles published in peer-reviewed journals since 1990 with the last search run on June 2014 and published in English language. The keyword search terms included: digital ulcer/s, systemic sclerosis, scleroderma, digital scars, ischemic complications, autoantibodies, biomarkers, endothelium dysfunction, endothelin-1, vascular endothelial growth factor (VEGF), endostatin, ADMA, endoglin, angiostatin, and capillaroscopy. The following criteria were included: (1) cohorts of SSc patients including patients with DU, (2) endothelium dysfunction and angiogenesis biomarkers compared with a healthy control group, (3) autoantibodies, capillary morphology and distribution, endothelium dysfunction and angiogenesis biomarkers compared between patients with and without digital ulcers, (4) detailed description of the statistical methods used to conclude for predictive factors, and (5) English language. Our search provided a total of 376 citations. Of these, 297 studies were discarded for not meeting the criteria proposed.
Topics: Autoantibodies; Humans; Practice Guidelines as Topic; Risk Factors; Scleroderma, Systemic; Ulcer; Vascular Endothelial Growth Factor A
PubMed: 25449678
DOI: 10.1016/j.autrev.2014.10.009 -
Experimental and Therapeutic Medicine Jun 2024Angiomotin (Amot) family members, including Amot, Amot-like protein 1 (Amotl1) and Amot-like protein 2 (Amotl2), have been found to interact with angiostatins. In... (Review)
Review
Angiomotin (Amot) family members, including Amot, Amot-like protein 1 (Amotl1) and Amot-like protein 2 (Amotl2), have been found to interact with angiostatins. In addition, Amot family members are involved in various physiological and pathological functions such as embryonic development, angiogenesis and tumorigenesis. Some studies have also demonstrated its regulation in signaling pathways such as the Hippo signaling pathway, AMPK signaling pathway and mTOR signaling pathways. Amot family members play an important role in neural stem cell differentiation, dendritic formation and synaptic maturation. In addition, an increasing number of studies have focused on their function in promoting and/or suppressing cancer, but the underlying mechanisms remain to be elucidated. The present review integrated relevant studies on upstream regulation and downstream signals of Amot family members, as well as the latest progress in physiological and pathological functions and clinical applications, hoping to offer important ideas for further research.
PubMed: 38766307
DOI: 10.3892/etm.2024.12546 -
Clinical and Experimental Rheumatology 2020To investigate serum levels of a panel of angiogenic inducers (VEGF, FGF-2, Angiopoietin 1, -2, soluble VCAM-1) and inhibitors (angiostatin, endostatin, pentraxin-3) in...
OBJECTIVES
To investigate serum levels of a panel of angiogenic inducers (VEGF, FGF-2, Angiopoietin 1, -2, soluble VCAM-1) and inhibitors (angiostatin, endostatin, pentraxin-3) in patients with giant cell arteritis (GCA) and Takayasu's arteritis (TAK), in order to gain further insights into the molecular mechanisms driving angiogenesis dysregulation in large-vessel vasculitis (LVV).
METHODS
Sera were obtained from 33 TAK patients and 14 GCA patients and from two groups of age-matched normal controls (NC). Disease activity was assessed using 18F-FDG PET/CT and clinical indices including NIH/Kerr criteria and ITAS. Angiogenic and anti-angiogenic factor serum levels were evaluated using commercial ELISA kits. Pentraxin 3 (PTX3) serum levels were evaluated by non-commercial ELISA, as already described.
RESULTS
Among the angiogenic factors, only VEGF serum levels were significantly higher in TAK patients compared to NC. No difference was found between angiogenic factor levels in GCA patients compared to those detected in NC. Anti-angiogenic factor (Angiostatin, Endostatin, PTX3) serum levels were significantly higher in both GCA and TAK patients compared to NC. Significant associations were observed between VEGF and PTX3 levels and disease activity evaluated using PET scan and clinical indices. Cluster analysis based on PET scan scores in TAK patients showed significant ordered differences in VEGF and angiostatin serum levels. Indeed, we noted a progressive increase of VEGF and angiostatin from NC to the cluster including patients with the highest and more diffuse scan positivity.
CONCLUSIONS
Our overall results demonstrate a circulating molecular profile characterised by a prevailing expression of anti-angiogenic soluble factors.
Topics: Angiogenic Proteins; Angiopoietin-1; Angiopoietin-2; Angiostatic Proteins; Angiostatins; C-Reactive Protein; Endostatins; Fibroblast Growth Factor 2; Giant Cell Arteritis; Humans; Neovascularization, Pathologic; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Serum Amyloid P-Component; Takayasu Arteritis; Vascular Cell Adhesion Molecule-1; Vascular Endothelial Growth Factor A
PubMed: 31573481
DOI: No ID Found -
Dermatologic Therapy Jan 2021Local angiogenesis accompanies inflammation in psoriasis-affected skin. To determine the serum concentrations of selected pro- and anti-angiogenic factors and their...
Local angiogenesis accompanies inflammation in psoriasis-affected skin. To determine the serum concentrations of selected pro- and anti-angiogenic factors and their interrelationships in patients with plaque psoriasis. The study included 41 men diagnosed with psoriasis, aged 43.5 ± 11.7 years. The Psoriasis Area and Severity Index score was 23.4 ± 5.2 points. The control group consisted of 38 healthy, age-matched men. The levels of pro-angiogenic cytokines and angiogenesis inhibitors, including fibroblast growth factor 1 (FGF-1), vascular endothelial growth factor A (VEGF-A), endostatin, and angiostatin, were determined from the serum of patients and controls using enzyme-linked immunosorbent assays. Compared with controls, patients with psoriasis had a significantly lower concentration of FGF-1 (P = .01) but higher concentrations of endostatin (P = .04) and angiostatin (P = .02). The concentration of VEGF-A was also higher in patients with psoriasis but not significantly (P = .25). The concentration of C-reactive protein (CRP) was significantly higher among patients with psoriasis than controls (P < .0001). Among controls, CRP concentrations did not correlate significantly with the concentrations of FGF-1, VEGF-A, endostatin, or angiostatin. Among patients with psoriasis, CRP concentrations correlated moderately with the concentrations of VEGF-A (r = .35; P = .02) and angiostatin (r = .31; P = .04). The concentration of VEGF-A correlated positively with PASI (r = .05; P = .0009) and BSA values (r = .39; P = .01). Psoriasis is associated with an altered systemic balance between pro-angiogenic and anti-angiogenic factors. The increase in serum angiogenesis inhibitors may be associated with unfavorable changes in the development of coronary collateral circulation. However, the clinical significance of this has not yet been established.
Topics: Adult; Angiogenic Proteins; Angiostatins; Endostatins; Fibroblast Growth Factor 1; Humans; Male; Middle Aged; Psoriasis; Skin; Vascular Endothelial Growth Factor A
PubMed: 33381893
DOI: 10.1111/dth.14727 -
Asian Pacific Journal of Tropical... Jun 2016To discuss the expression and significance of angiostatin, vascular endothelial growth factor and matrix metalloproteinase-9 in the brain tissue of diabetic rats with...
OBJECTIVE
To discuss the expression and significance of angiostatin, vascular endothelial growth factor and matrix metalloproteinase-9 in the brain tissue of diabetic rats with ischemia reperfusion.
METHODS
A total of 60 male Wistar rats were randomly divided into the normal group, sham group, diabetic cerebral infarction group and single cerebral infarction group according to the random number table, with 15 rats in each group. The high sucrose diet and intraperitoneal injection of streptozotocin were performed for the modeling of diabetic rats, while the thread-occlusion method was employed to build the model of cerebral ischemia reperfusion. The immunohistochemical staining was performed to detect the expression of angiostatin, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in the brain tissue.
RESULTS
The expression of angiostatin after the reperfusion in the brain tissue of rats in the single cerebral infarction group and diabetic cerebral infarction group was increased 6 h after the reperfusion, reached to the peak on 1 d and then decreased gradually. The expression of angiostatin in the diabetic cerebral infarction group 6 h, 1 d, 3 d and 7 d after the reperfusion was significantly higher than that in the single cerebral infarction group (P < 0.05). VEGF began to be increased 1 h after the reperfusion in the single cerebral infarction group and diabetic cerebral infarction group, reached to the peak at 6 h and then decreased gradually. The expression of VEGF in the diabetic cerebral infarction group at each time point after the reperfusion was significantly lower than that in the single cerebral infarction group (P < 0.05). MMP-9 began to be increased 1 h after the reperfusion in the single cerebral infarction group and diabetic cerebral infarction group, reached to the peak on 1 d and then decreased gradually. The expression of MMP-9 in the diabetic cerebral infarction group at each time point after the reperfusion was significantly higher than that in the single cerebral infarction group (P < 0.05).
CONCLUSIONS
The high glucose environment in which the diabetic cerebral infarction is occurred is to induce the formation of MMP-9 at first and then activate and increase the expression of angiostatin. Afterwards, the expression of VEGF is inhibited, resulting in the poor angiogenesis after cerebral infarction, which thus makes the injury of brain tissue after cerebral infarction even worse than the non-diabetes mellitus.
PubMed: 27262072
DOI: 10.1016/j.apjtm.2016.04.001 -
Frontiers in Cardiovascular Medicine 2018Fabry disease (FD) is characterized by early development of vasculopathy and endothelial dysfunction. However, it is unclear whether these findings also play a pivotal...
Fabry disease (FD) is characterized by early development of vasculopathy and endothelial dysfunction. However, it is unclear whether these findings also play a pivotal role in cardiac manifestation. As Fabry cardiomyopathy (FC) is the leading cause of death in FD, we aimed to gather a better insight in pathological mechanisms of the disease. Serum samples were obtained from 17 healthy controls, 15 FD patients with and 7 without FC. FC was defined by LV wall thickening of >12 mm in cardiac magnetic resonance imaging and serum level of proBNP, high sensitive Troponin T (hsT), and globotriaosylsphingosine (lyso-GB3) were obtained. A multiplex ELISA-Assay for 23 different angiogenesis markers was performed in pooled samples. Markers showing significant differences among groups were further analyzed in single samples using specific Elisa antibody assays. L-homoarginine (hArg), L-arginine, asymmetric (ADMA), and symmetric Dimethylarginine (SDMA) were quantified by liquid chromatography-mass spectrometry. Angiostatin and matrix metalloproteinase 9 (MMP-9) were elevated in FD patients compared to controls independently of the presence of FC (angiostatin: 98 ± 25 vs. 75 ± 15 ng/mL; = 0.001; MMP-9: 8.0 ± 3.4 vs. 5.0 ± 2.4 μg/mL; = 0.002). SDMA concentrations were highest in patients with FC (0.90 ± 0.64 μmol/l) compared to patients without (0.57 ± 0.10 μmol/l; = 0.027) and vs. controls (0.58 ± 0.12 μmol/l; = 0.006) and was positively correlated with indexed LV-mass ( = 0.61; = 0.003), hsT ( = 0.56, = 0.008), and lyso-Gb3 ( = 0.53, = 0.013). Accordingly, the ratio of L-homoarginine to SDMA (hArg/SDMA) was lowest in patients with FC (2.63 ± 1.78) compared to controls (4.16 ± 1.44; = 0.005). For L-arginine, hArg and ADMA no significant differences among groups could be detected, although a trend toward higher ADMA and lower hArg levels could be observed in the FC group. Furthermore, a significant relationship between kidney and cardiac function could be revealed ( = 0.045). Elevated MMP-9 and angiostatin levels suggest an increased extracellular matrix turnover in FD patients. Furthermore, endothelial dysfunction may also be involved in FC, as SDMA and hArg/SDMA are altered in these patients.
PubMed: 30159316
DOI: 10.3389/fcvm.2018.00108 -
FASEB Journal : Official Publication of... May 2021Cold atmospheric plasma (CAP) is an emerging technology for biomedical applications, exemplified by its antimicrobial and antineoplastic potentials. On the contrary,...
Cold atmospheric plasma (CAP) is an emerging technology for biomedical applications, exemplified by its antimicrobial and antineoplastic potentials. On the contrary, acidic fibroblast growth factor (aFGF) has been a long-standing potent mitogen for cells from various origins. In this study, we are the first to develop a multimodal treatment combining the aforementioned physicochemical and pharmacological treatments and investigated their individual and combined effects on wound healing, angiogenesis, neurogenesis, and osteogenesis. This work was performed at the tissue, cellular, protein, and gene levels, using histochemical staining, flow cytometry, ELISA, and PCR, respectively. Depending on the type of target tissue, various combinations of aforementioned methods were used. The results showed that the enhancement on would healing and angiogenesis by CAP and aFGF were synergistic. The former was manifested by increased murine fibroblast proliferation and reduced cutaneous tissue inflammation, whereas the latter by upregulated proangiogenic markers in vivo, for example, CD31, VEGF, and TGF-β, and downregulated antiangiogenic proteins in vitro, for example, angiostatin and angiopoietin-2, respectively. In addition, aFGF outperformed CAP during neurogenesis, which was evidenced by superior neurite outgrowth, while CAP exceeded aFGF in osteogenesis which was demonstrated by more substantial bone nodule formation. These novel findings not only support the fact that CAP and aFGF are both multipotent agents during tissue regeneration, but also highlight the potential of our multimodal treatment combining the individual advantages of CAP and aFGF. The versatile administration route, that is, topical and/or systemic, might further broaden its applications.
Topics: Animals; Atmosphere; Combined Modality Therapy; Fibroblast Growth Factor 1; Humans; Mice; Neovascularization, Physiologic; Neurogenesis; Plasma Gases; Regeneration; Wound Healing
PubMed: 33774850
DOI: 10.1096/fj.202002611R -
Physiological Reports Jun 2020Ozone is a toxic and highly reactive gaseous oxidizing chemical with well-documented adverse health effects in humans. On the basis of animal and human data,...
Ozone is a toxic and highly reactive gaseous oxidizing chemical with well-documented adverse health effects in humans. On the basis of animal and human data, environmental guidelines and air quality standards recommend a threshold for exposure of no more than 0.063 ppm of ozone (daily concentrations). This research describes a standardized sensitive model of sterile murine lung inflammation induced by exposing mice to acute (0, 4 or 24 hr), yet low, levels of ozone (0.005, 0.05 or 0.5 ppm), one that are below the current recommendations for what is considered a safe or "ambient" ozone concentration for humans. Ozone led to concentration and time-dependent phlogistic cell death in the bronchoalveolar lavage, lung epithelial damage and hemorrhage. Interestingly, we observed distinct large bright CD11b positive cells in the bronchoalveolar lavage, upregulation of lung vascular and alveolar ATP synthase as well as plasminogen and bronchiolar angiostatin expression in ozone-exposed mice, platelet and neutrophil accumulation in the lung vasculature and an eotaxin-2, IL-16, CXCL5, CXCL12, and CXCL13 dominant inflammatory response leading to lung injury. Using a fluorescent intravital microscopy set up, we quantified ozone-induced extensive alveolar cellular damage. We observed ozone-induced actin filament disorganization, perturbed respiratory mechanics, acute suppression of the alveolar reactive oxygen species (ROS) production and mitochondrial potential in ventilated lungs. We present evidence of systemic, as well as pulmonary toxicity, at 40-fold lower ozone concentrations than previously reported in mice. The findings are important in establishing a sensitive means of quantifying structural and functional lung disorganization following exposure to an aerosolized pollutant, even at levels of ozone exposure previously thought to be safe in humans.
Topics: Acute Lung Injury; Animals; Inflammation Mediators; Male; Mice, Inbred C57BL; Ozone; Pneumonia
PubMed: 32524776
DOI: 10.14814/phy2.14463