scholarly journals An interplay of microglia and matrix metalloproteinase MMP9 under hypoxic stress regulates the opticin expression in retina

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Satish Patnaik ◽  
Meenakshi Rai ◽  
Subhadra Jalali ◽  
Komal Agarwal ◽  
Akshay Badakere ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Vascular Diseases ◽  
Vascular Endothelial ◽  
Microglia Cell ◽  
Human Microglia ◽  
Complement Component C3 ◽  
Inflammatory Proteins ◽  
Preterm Born ◽  
Endothelial Growth Factor ◽  
Increased Activity

AbstractInflammation plays a key role in the pathogenesis of retinal vascular diseases. We have shown earlier an increase in the activity of matrix metalloproteinases in the vitreous and tears of preterm born babies with retinopathy of prematurity (ROP) compared to those with no-ROP leading to a shift in the balance of angiogenic (vascular endothelial growth factor [VEGF], matrix metalloproteinase [MMPs], complement component [C3]) and anti-angiogenic (opticin, thrombospondin) in ROP eyes. We now confirmed that tear MMP levels in premature infants perfectly correlates with disease severity. Next, we demonstrated that a reduced opticin levels in ROP vitreous are regulated by MMPs secreted by activated microglia. Upon exposing the human microglia cell line (CHME3) to hypoxia, an increased expression of inflammatory proteins (MMP9, VEGF) was noticed while opticin reduced significantly (p = 0.005). Further, the reduced opticin’s expression by microglial cells under hypoxia could be rescued by inhibiting the MMP activity using doxycycline and EDTA. The inhibition of MMP activity altered the expression of other key signaling molecules under hypoxia. Our study clearly explains that increased activity of MMPs under hypoxia regulates the expression of opticin as seen in the vitreous humor of ROP and could serve as a potential target for ROP management.

scholarly journals Human Plasma Levels of Vascular Endothelial Growth Factor, Matrix Metalloproteinase 9, and Tissue Inhibitor of Matrix Metalloproteinase 1 and Their Applicability as Tumor Markers in Diagnoses of Cervical Cancer Based on ROC Analysis

2018 ◽  
Vol 25 (1) ◽  
pp. 107327481878935 ◽  
Author(s):  
Monika Zajkowska ◽  
Monika Zbucka-Krętowska ◽  
Iwona Sidorkiewicz ◽  
Emilia Lubowicka ◽  
Grażyna Ewa Będkowska ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Matrix Metalloproteinase ◽  
Plasma Levels ◽  
Statistical Significance ◽  
Ca 125 ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor ◽  
Metalloproteinase 9

Cervical cancer (CC) remains a major diagnostic problem. The introduction of human papillomavirus vaccination significantly reduced the number of new cases; however, the search for new methods that would earlier indicate the development of cancerous changes is vital. The aim of this study was to investigate the diagnostic power of those parameters in comparison to Cancer Antigen 125 (CA 125) and Squamous Cell Carcinoma Antigen (SCC-Ag) in patients with CC and in relation to the control group. The study included 100 patients with CC and 50 healthy women. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay, CA 125, and SCC-Ag by chemiluminescent microparticle immunoassay. Plasma levels of all parameters in the total cancer group showed statistical significance (in all cases P < .05). In stage I cancer, only vascular endothelial growth factor (VEGF) and tissue inhibitors of metalloproteinase 1; in stage II, all the tested parameters and CA 125; and in stage III + IV, VEGF, matrix metalloproteinase 9 (MMP-9), and CA 125 showed statistical significance when compared to the healthy volunteers group. Vascular endothelial growth factor showed the highest value of sensitivity from all tested parameters (I: 75%, II: 76%, III + IV: 94%, and 82% in total CC group). The highest specificity was obtained by MMP-9 (94%). In the total CC, stage I, and stage II groups, all tested parameters showed statistically significant area under the receiver operating characteristics curve (AUC), but maximum range was obtained for the combination VEGF + SCC-Ag (I: 0.9146, II: 0.8941, III + IV: 0.9139, total CC group: 0.9347). The combined analysis of tested parameters and tumor markers resulted in an increase in sensitivity and AUC values, which provides hope for developing new panel of biomarkers that may be used in the diagnosis of CC in the future.

Expression of Vascular Endothelial Growth Factor, Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 in Polycystic Ovarian Syndrome Rats and Its Implication

2021 ◽  
Vol 11 (5) ◽  
pp. 841-846
Author(s):  
Wei Li ◽  
Yufang Zhang ◽  
Fuping Li ◽  
Yufen Shi ◽  
Yan Wang
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Matrix Metalloproteinase ◽  
Polycystic Ovary ◽  
Ovarian Tissue ◽  
Matrix Metalloproteinase 2 ◽  
Control Group ◽  
Vaginal Smear ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Polycystic ovary syndrome (PCOS) is a female endocrine disorder and frequently leads to infertility. Vascular endothelial growth factor (VEGF) has crucial roles and matrix metalloproteinase (MMPs) is correlated with cell migration. Both of them are involved in the occurrence and progression of PCOS. This study established a rat PCOS model using letrozole to measure the expression of VEGF, MMP-2 and MMP-9 (MMP-2/9), to analyze its correlation with PCOS. Letrozole was applied by gavage to establish rat PCOS model. General condition and ovarian tissue morphology were observed under a light field microscope. ELISA and immunohistochemistry (IHC) were used to detect serum or tissue expression of VEGF, MMP-2/9. Estrous cycle of rats was disrupted after 12 d for using letrozole. Vaginal smear showed abundant leukocytes with sparse keratinocytes. Ovary showed whitening and increased volume, with early phase small follicles plus lower granular cells or corpus luteum. Compared to control group, experimental group had significantly higher VEGF, MMP-2/9 (P < 0.05), which were higher in antral follicles than those in preantral follicle with higher expressions than primordial follicle (P < 0.05). In conclusion, VEGF, MMP-2/9 are abundantly expressed in both serum and tissues of PCOS rats.

scholarly journals Cardiac structural and hemodynamic changes associated with physiological heart hypertrophy of pregnancy are reversed postpartum

2012 ◽  
Vol 113 (8) ◽  
pp. 1253-1259 ◽  
Author(s):  
Soban Umar ◽  
Rangarajan Nadadur ◽  
Andrea Iorga ◽  
Marjan Amjedi ◽  
Humann Matori ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Matrix Metalloproteinase ◽  
Cardiac Fibrosis ◽  
Matrix Metalloproteinase 2 ◽  
Heart Weight ◽  
Vascular Endothelial ◽  
Heart Hypertrophy ◽  
Hemodynamic Changes ◽  
Endothelial Growth Factor

Pregnancy is associated with ventricular hypertrophy and volume overload. Here we investigated whether late pregnancy is associated with cardiac structural and hemodynamic changes, and if these changes are reversed postpartum. Female mice (C57BL/6) were used in nonpregnant diestrus (NP), late-pregnant (LP), or 7-day postpartum (PP7) stages. Echocardiography and cardiac catheterization were performed to monitor cardiac hemodynamics. Transcript expression of proangiogenic vascular endothelial growth factor, cardiac fetal gene osteopontin, cardiac extracellular matrix-degrading enzymes matrix metalloproteinase-2, and a disintegrin and metalloproteinase-15 and -17 were assessed by RT-PCR. Masson trichrome staining for cardiac fibrosis and endothelial marker CD31 immunostaining for angiogenesis were performed. Heart hypertrophy in LP was fully reversed in PP7 (heart weight: NP = 114 ± 4 mg; LP = 147 ± 2 mg; PP7 = 117 ± 8 mg, P < 0.05 for LP vs. PP7). LP had elevated left ventricular (LV) pressure (119 ± 5 mmHg in LP vs. 92 ± 7 mmHg in NP, P < 0.05) that was restored at PP7 (95 ± 8 mmHg, P < 0.001 vs. LP). LP had increased LV contractility (maximal rate of increase of LV pressure = 6,664 ± 297 mmHg/s in LP vs. 4,294 ± 568 mmHg/s in NP, P < 0.01) that was restored at PP7 (5,313 ± 636 mmHg/s, P < 0.05 vs. LP). LV ejection fraction was reduced in LP (LP = 58 ± 1% vs. NP = 70 ± 4%, P < 0.001) and was already restored at PP1 (77 ± 2%, P < 0.001 vs. LP). Myocardial angiogenesis was significantly increased in LP (capillary density = 1.25 ± 0.02 vs. 0.95 ± 0.01 capillaries/myocyte in NP, P < 0.001) and was fully restored in PP7 (0.98 ± 0.01, P < 0.001 vs. LP). Vascular endothelial growth factor was upregulated in LP (LP = 1.4 ± 0.1 vs. NP = 1 ± 0.1, normalized to NP, P < 0.001) and was restored in PP7 (PP7 = 0.83 ± 0.1, P < 0.001 vs. LP). There was no increase in cardiac fibrosis in LP. Matrix metalloproteinase-2 transcript levels were downregulated in LP (LP = 0.47 ± 0.03 vs. NP = 1 ± 0.01, normalized to NP, P < 0.001) and was restored at PP7 (0.70 ± 0.1, P < 0.001 vs. LP). In conclusion, pregnancy-induced heart hypertrophy is associated with transient cardiac dysfunction, increased cardiac angiogenesis, lack of fibrosis, and decreased expression of remodeling enzymes that are reversed postpartum.

scholarly journals Therapies for Neovascular Age-Related Macular Degeneration: Current Approaches and Pharmacologic Agents in Development

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Mostafa Hanout ◽  
Daniel Ferraz ◽  
Mehreen Ansari ◽  
Natasha Maqsood ◽  
Saleema Kherani ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Vascular Diseases ◽  
Age Related Macular Degeneration ◽  
Treatment Modalities ◽  
Vascular Endothelial ◽  
New Therapies ◽  
Age Related ◽  
Early Phase Clinical Trials ◽  
Endothelial Growth Factor ◽  
Pharmacologic Agents

As one of the leading causes of blindness, age-related macular degeneration (AMD) has remained at the epicenter of clinical research in ophthalmology. During the past decade, focus of researchers has ranged from understanding the role of vascular endothelial growth factor (VEGF) in the angiogenic cascades to developing new therapies for retinal vascular diseases. Anti-VEGF agents such as ranibizumab and aflibercept are becoming increasingly well-established therapies and have replaced earlier approaches such as laser photocoagulation or photodynamic therapy. Many other new therapeutic agents, which are in the early phase clinical trials, have shown promising results. The purpose of this paper is to briefly review the available treatment modalities for neovascular AMD and then focus on promising new therapies that are currently in various stages of development.

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