scholarly journals Transgenic overexpression of macrophage matrix metalloproteinase-9 exacerbates age-related cardiac hypertrophy, vessel rarefaction, inflammation, and fibrosis

2017 ◽  
Vol 312 (3) ◽  
pp. H375-H383 ◽  
Author(s):  
Hiroe Toba ◽  
Presley L. Cannon ◽  
Andriy Yabluchanskiy ◽  
Rugmani Padmanabhan Iyer ◽  
Jeanine D’Armiento ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Cardiac Hypertrophy ◽  
Matrix Metalloproteinase 9 ◽  
Elderly Subjects ◽  
Related Factors ◽  
Cross Sectional ◽  
Cardiac Aging ◽  
Cardiac Inflammation ◽  
Age Related ◽  
Metalloproteinase 9

Advancing age is an independent risk factor for cardiovascular disease. Matrix metalloproteinase-9 (MMP-9) is secreted by macrophages and robustly increases in the left ventricle (LV) with age. The present study investigated the effect of MMP-9 overexpression in macrophages on cardiac aging. We compared 16- to 21-mo-old C57BL/6J wild-type (WT) and transgenic (TG) male and female mice ( n = 15–20/group). MMP-9 overexpression amplified the hypertrophic response to aging, as evidenced by increased LV wall thickness and myocyte cross-sectional areas ( P < 0.05 for both). MMP-9 overexpression reduced LV expression of the angiogenesis-related factors ICAM-1, integrins α3 and β3, platelet/endothelial cell adhesion molecule-1, thrombospondin-1, tenascin-c, and versican (all P < 0.05). Concomitantly, the number of vessels in the TG was lower than WT LV ( P < 0.05). This led to a mismatch in the muscle-to-vessel ratio and resulted in increased cardiac inflammation. Out of 84 inflammatory genes analyzed, 16 genes increased in the TG compared with WT (all P < 0.05). Of the elevated genes, 14 were proinflammatory genes. The increase in cardiac inflammation resulted in greater accumulation of interstitial collagen in TG ( P < 0.05). Fractional shortening was similar between groups, indicating that global cardiac function was still preserved at this age. In conclusion, overexpression of MMP-9 in macrophages resulted in exacerbated cardiac hypertrophy in the setting of vessel rarefaction, which resulted in enhanced inflammation and fibrosis to augment the cardiac-aging phenotype. Our results provide evidence that macrophage-derived MMP-9 may be a therapeutic target in elderly subjects. NEW & NOTEWORTHY The present study was the first to use mice with transgenic overexpression of matrix metalloproteinase-9 (MMP-9) in macrophages to examine the effects of macrophage-derived MMP-9 on cardiac aging. We found that an elevation in macrophage-derived MMP-9 induced a greater age-dependent cardiac hypertrophy and vessel rarefaction phenotype, which enhanced cardiac inflammation and fibrosis. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/macrophage-mmp-9-accelerates-cardiac-aging/ .

scholarly journals Cardiac aging is initiated by matrix metalloproteinase-9-mediated endothelial dysfunction

2014 ◽  
Vol 306 (10) ◽  
pp. H1398-H1407 ◽  
Author(s):  
Andriy Yabluchanskiy ◽  
Yonggang Ma ◽  
Ying Ann Chiao ◽  
Elizabeth F. Lopez ◽  
Andrew P. Voorhees ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Vascular Permeability ◽  
Oxygen Demand ◽  
Matrix Metalloproteinase 9 ◽  
Lv Function ◽  
Proteomic Profiling ◽  
Cross Sectional ◽  
Cardiac Aging ◽  
Myocyte Hypertrophy ◽  
Metalloproteinase 9

Aging is linked to increased matrix metalloproteinase-9 (MMP-9) expression and extracellular matrix turnover, as well as a decline in function of the left ventricle (LV). Previously, we demonstrated that C57BL/6J wild-type (WT) mice > 18 mo of age show impaired diastolic function, which was attenuated by MMP-9 deletion. To evaluate mechanisms that initiate the development of cardiac dysfunction, we compared the LVs of 6–9- and 15–18-mo-old WT and MMP-9 null (Null) mice. All groups showed similar LV function by echocardiography, indicating that dysfunction had not yet developed in the older group. Myocyte nuclei numbers and cross-sectional areas increased in both WT and Null 15–18-mo mice compared with young controls, indicating myocyte hypertrophy. Myocyte hypertrophy leads to an increased oxygen demand, and both WT and Null 15–18-mo mice showed an increase in angiogenic signaling. Plasma proteomic profiling and LV analysis revealed a threefold increase in von Willebrand factor and fivefold increase in vascular endothelial growth factor in WT 15–18-mo mice, which were further elevated in Null mice. In contrast to the upregulation of angiogenic stimulating factors, actual LV vessel numbers increased only in the 15–18-mo Null LV. The 15–18-mo WT showed amplified expression of inflammatory genes related to angiogenesis, including C-C chemokine receptor (CCR)7, CCR10, interleukin (IL)-1f8, IL-13, and IL-20 (all, P < 0.05), and these increases were blunted by MMP-9 deletion (all, P < 0.05). To measure vascular permeability as an index of endothelial function, we injected mice with FITC-labeled dextran. The 15–18-mo WT LV showed increased vascular permeability compared with young WT controls and 15–18-mo Null mice. Combined, our findings revealed that MMP-9 deletion improves angiogenesis, attenuates inflammation, and prevents vascular leakiness in the setting of cardiac aging.

scholarly journals Expression of Matrix Metalloproteinase-9 in Different Histopathological Variants of Ameloblastoma: A Cross-sectional Study

2021 ◽  
Author(s):  
Revati Shailesh Deshmukh ◽  
Priya Nimish Deo ◽  
Surekha Laxman Chavan ◽  
Prasad Kango
Keyword(s):  
Matrix Metalloproteinase ◽  
Tumour Progression ◽  
Matrix Metalloproteinase 9 ◽  
High Rate ◽  
P Value ◽  
Biological Behaviour ◽  
Cross Sectional ◽  
Intense Staining ◽  
Variable Expression ◽  
Metalloproteinase 9

Introduction: Ameloblastomas are benign and the most common odontogenic neoplasms with many histopathological subtypes depending on the predominant pattern. They are known for their aggressive behaviour. As ameloblastomas have a high rate of recurrence, it is necessary to understand the biological behaviour of these neoplasms. Matrix Metalloproteinase-9 (MMP-9) is an enzyme that belongs to Metalloproteinases family and is known to degrade the Extracellular Matrix (ECM) and facilitate tumour progression. Evaluation of the expression of MMP-9 in ameloblastomas could contribute in understanding its biological behaviour. Aim: To analyse the expression of MMP-9 in different histopathological variants of ameloblastoma. Materials and Methods: A cross-sectional observational study was done in the Department of Oral Pathology and Microbiology, Bharati Vidyapeeth Deemed to be University, Dental College and Hospital, Pune, India. A total of 30 cases were selected for this study. The study was carried out for a duration of two years from April 2018 to April 2020. The MMP-9 expression was studied by immunohistochemical staining. The statistical comparison was done using Chi-square test between groups, p-value <0.05 was considered significant. The data was statistically analysed using Statistical Package for Social Sciences (SPSS) version 22.0, IBM Corporation, USA for MS Windows. Results: A total of 30 paraffin embedded archival tissue blocks were selected for this study. Among them nine cases were of Plexiform Ameloblastoma, eight of Unicystic Ameloblastoma, three of Acanthomatous Ameloblastoma, four of Desmoplastic Ameloblastoma and six were of Follicular Ameloblastomas. The MMP-9 showed variable expression in different histopathological subtypes of ameloblastoma. This difference was statistically significant between Plexiform and Acanthomatous as well as Plexiform and Follicular variants (p<0.05). A 66.7% (6 out of 9 samples) of Plexiform Ameloblastoma showed intense staining for MMP-9. Conclusion: Expression of MMP-9 varies in different histopathological variants of ameloblastoma and may not have an association with biological behaviour and aggressiveness.

scholarly journals Association of tear matrix metalloproteinase 9 immunoassay with signs and symptoms of dry eye disease: A cross-sectional study using qualitative, semiquantitative, and quantitative strategies

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258203
Author(s):  
You Hyun Lee ◽  
Seung-Pil Bang ◽  
Kyu-Young Shim ◽  
Myung-Jin Son ◽  
Harim Kim ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Dry Eye ◽  
Signs And Symptoms ◽  
Cross Sectional Study ◽  
Matrix Metalloproteinase 9 ◽  
Sectional Study ◽  
Cross Sectional ◽  
Staining Score ◽  
Corneal Staining ◽  
Metalloproteinase 9

Purpose This study aimed to analyze the association of tear matrix metalloproteinase 9 (MMP-9) immunoassay with the severity of dry eye (DE) signs and symptoms through qualitative, semiquantitative, and quantitative evaluations of immunoassay band. Materials and methods This cross-sectional study enrolled 320 eyes of 320 patients. The clinical signs of DE were assessed using the Ocular Surface Disorder Index (OSDI) score, visual analogue scale (VAS), tear breakup time (tBUT), tear volume evaluation by tear meniscometry, and staining scores of the cornea and conjunctiva by the Oxford grading scheme. The tear MMP-9 immunoassay results were interpreted using qualitative (positive or negative), semi-quantitative (reagent band density on a four-point scale: 0 = negative; 1 = weakly positive; 2 = moderately positive; 3 = strongly positive), and quantitative (ratio of reagent band density to control band density) indicators. Results Positive MMP-9 immunoassay results were significantly related to shorter tBUT, tBUT ≤3 seconds, higher corneal staining score, corneal staining score ≥2, and conjunctival staining score ≥2. The semi-quantitative results of the MMP-9 immunoassay were positively correlated with higher corneal staining score (r = 0.122, p = 0.029) and negatively correlated with tBUT (r = -0.125, p = 0.025). However, in the quantitative analysis, none of the DE signs or symptoms were correlated to the band density of the MMP-9 immunoassay. Conclusions The positive MMP-9 immunoassay results were related to the severity of ocular signs of DE. However, using quantitative measures of the MMP-9 immunoassay to assess the clinical severity of DE requires further investigation.

scholarly journals Urinary Matrix Metalloproteinase-9 and Nephrin in Idiopathic Membranous Nephropathy: A Cross-Sectional Study

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Akankwasa Gilbert ◽  
An Changjuan ◽  
Cheng Guixue ◽  
Liu Jianhua ◽  
Qin Xiaosong
Keyword(s):  
Matrix Metalloproteinase ◽  
Membranous Nephropathy ◽  
Healthy Subjects ◽  
Kidney Injury ◽  
Matrix Metalloproteinase 9 ◽  
Idiopathic Membranous Nephropathy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cross Sectional ◽  
Glomerular Diseases ◽  
Metalloproteinase 9

Aim. Idiopathic membranous nephropathy (IMN) has a varied clinical course that requires accurate prediction as a prerequisite for treatment administration. Currently, its prognosis relies on proteinuria, a clinical parameter whose onset lags behind kidney injury. Increased urinary excretion of matrix metalloproteinase-9 (MMP-9) and nephrin has been reported in a number of IMN-like glomerular diseases in which they reflected disease severity. However, little or nothing is known of the importance of these biomarkers in IMN, a major cause of adult nephrotic syndrome. To highlight their potential, we measured both biomarkers and assessed their relationships with key parameters of renal function in IMN. Methods. We quantified urinary MMP-9 and nephrin in 107 biopsy-proven IMN patients and 70 healthy subjects by enzyme-linked immunosorbent assay (ELISA). We then compared biomarker levels between patients and healthy subjects and among patients with different clinical features. We also determined the relationship of each biomarker with proteinuria and the estimated glomerular filtration rate (eGFR). Results. Urinary MMP-9 and nephrin were significantly higher in IMN compared to healthy controls. Unlike nephrin, MMP-9 correlated significantly with proteinuria and was significantly higher among patients with nephrotic range proteinuria. Both biomarkers were correlated with eGFR, but only MMP-9 was significantly higher in patients with eGFR less than 90 ml/min/1.73 m2. Conclusion. Our findings suggest that urinary MMP-9 holds a greater potential than urinary nephrin in monitoring the severity of IMN.

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