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

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.

2012 ◽  
Vol 113 (8) ◽  
pp. 1253-1259 ◽  
Author(s):  
Soban Umar ◽  
Rangarajan Nadadur ◽  
Andrea Iorga ◽  
Marjan Amjedi ◽  
Humann Matori ◽  
...  

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.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Alena Chumanevich ◽  
Piper Wedman ◽  
Carole A. Oskeritzian

Mast cells (MC) are present in most vascularized tissues around the vasculature likely exerting immunomodulatory functions. Endowed with diverse mediators, resident MC represent first-line fine-tuners of local microenvironment. Sphingosine-1-phosphate (S1P) functions as a pluripotent signaling sphingolipid metabolite in health and disease. S1P formation occurs at low levels in resting MC and is upregulated upon activation. Its export can result in type 2 S1P receptor- (S1PR2-) mediated stimulation of MC, further fueling inflammation. However, the role of S1PR2 ligation in proangiogenic vascular endothelial growth factor- (VEGF-) A and matrix metalloproteinase- (MMP-) 2 release from MC is unknown. Using a preclinical MC-dependent model of acute allergic responses andin vitrostimulated primary mouse bone marrow-derived MC (BMMC) or human primary skin MC, we report that S1P signaling resulted in substantial amount of VEGF-A release. Similar experiments usingS1pr2-deficient mice or BMMC or selective S1P receptor agonists or antagonists demonstrated that S1P/S1PR2 ligation on MC is important for VEGF-A secretion. Further, we show that S1P stimulation triggered transcriptional upregulation of VEGF-A and MMP-2 mRNA in human but not in mouse MC. S1P exposure also triggered MMP-2 secretion from human MC. These studies identify a novel proangiogenic axis encompassing MC/S1P/S1PR2 likely relevant to inflammation.


2007 ◽  
Vol 121 (12) ◽  
pp. 1177-1183 ◽  
Author(s):  
P Dong ◽  
X Li ◽  
Z Yu ◽  
G Lu

AbstractObjective:To determine the correlation between expression of cyclooxygenase-2, vascular endothelial growth factor and matrix metalloproteinase-2, in patients with laryngeal carcinoma.Design:The study included 85 primary laryngeal squamous cell carcinoma cases. Expression was assessed using Envision immunohistochemical stains for cyclooxygenase-2, vascular endothelial growth factor and matrix metalloproteinase-2.Subjects:A tissue microarray containing samples from the 85 primary laryngeal squamous cell carcinoma cases was assembled. Immunohistochemical testing for cyclooxygenase-2, vascular endothelial growth factor and matrix metalloproteinase-2 was performed. Using Pearson correlation, expression of these proteins was compared with the following clinicopathological variables: age, sex, clinical tumour–node–metastasis staging, and prognosis. Three-year survival curves, factored by cyclooxygenase-2, vascular endothelial growth factor and matrix metalloproteinase-2 expression, were generated for overall survival, by Kaplan–Meier analysis.Results:The expression of cyclooxygenase-2 significantly differed between patients with different pathology, tumour–node–metastasis stage and prognosis. A marked difference in vascular endothelial growth factor expression was seen between two histological grade groups. Expression of matrix metalloproteinase-2 protein statistically significantly differed between patients with different tumour–node–metastasis stages, lymph node metastases and three-year survival rates. The expression of cyclooxygenase-2 in laryngeal carcinoma tissue was found to be associated with the expression of matrix metalloproteinase-2.Conclusion:Cyclooxygenase-2 and matrix metalloproteinase-2 may act as clinical prognostic indicators of tumour growth and differentiation in laryngeal carcinoma.


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