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Relationship between vitreous levels of matrix metalloproteinases and vascular endothelial growth factor in proliferative diabetic retinopathy
To investigate which matrix metalloproteinases (MMPs) are more likely to be involved in the angiogenic process in proliferative diabetic retinopathy (PDR), we measured the levels of MMPs in the vitreous fluid from patients with PDR and controls and correlated these levels with the levels of vascular...
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Published in: | PloS one 2013-12, Vol.8 (12), p.e85857-e85857 |
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description | To investigate which matrix metalloproteinases (MMPs) are more likely to be involved in the angiogenic process in proliferative diabetic retinopathy (PDR), we measured the levels of MMPs in the vitreous fluid from patients with PDR and controls and correlated these levels with the levels of vascular endothelial growth factor (VEGF). Vitreous samples from 32 PDR and 24 nondiabetic patients were studied by mosaic multiplex MMPs enzyme-linked immunosorbent assay (ELISA), single ELISA, Western blot and zymography analysis. Epiretinal membranes from 11 patients with PDR were studied by immunohistochemistry. MMP-8 and MMP-13 were not detected. ELISA, Western blot and gelatin ymography assays revealed significant increases in the expression levels of MMP-1, MMP-7, MMP-9 and VEGF in vitreous samples from PDR patients compared to nondiabetic controls, whereas MMP-2 and MMP-3 were not upregulated in vitreous samples from PDR patients. Significant correlations existed between ELISA and zymography assays for the quantitation of MMP-2 (r=0.407; p=0.039) and MMP-9 (r=0.711; p |
doi_str_mv | 10.1371/journal.pone.0085857 |
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Vitreous samples from 32 PDR and 24 nondiabetic patients were studied by mosaic multiplex MMPs enzyme-linked immunosorbent assay (ELISA), single ELISA, Western blot and zymography analysis. Epiretinal membranes from 11 patients with PDR were studied by immunohistochemistry. MMP-8 and MMP-13 were not detected. ELISA, Western blot and gelatin ymography assays revealed significant increases in the expression levels of MMP-1, MMP-7, MMP-9 and VEGF in vitreous samples from PDR patients compared to nondiabetic controls, whereas MMP-2 and MMP-3 were not upregulated in vitreous samples from PDR patients. Significant correlations existed between ELISA and zymography assays for the quantitation of MMP-2 (r=0.407; p=0.039) and MMP-9 (r=0.711; p<0.001). Significant correlations were observed between levels of VEGF and levels of MMP-1 (r=0.845; P<0.001) and MMP-9 (r=0.775; p<0.001), and between levels of MMP-1 and MMP-9 (r=0.857; p<0.001). In epiretinal membranes, cytoplasmic immunoreactivity for MMP-9 was present in vascular endothelial cells and stromal monocytes/macrophages and neutrophils. Our findings suggest that among the MMPs measured, MMP-1 and MMP-9 may contribute to the angiogenic switch in PDR.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0085857</identifier><identifier>PMID: 24392031</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Angiogenesis ; Assaying ; Cancer ; Cell adhesion & migration ; Collagenase 3 ; Consent ; Correlation ; Diabetes ; Diabetes mellitus ; Diabetic retinopathy ; Diabetic Retinopathy - complications ; Diabetic Retinopathy - enzymology ; Diabetic Retinopathy - metabolism ; Diabetic Retinopathy - pathology ; Endothelial cells ; Enzyme-linked immunosorbent assay ; Enzymes ; Gelatin ; Gelatinase A ; Gelatinase B ; Hemorrhage ; Histology ; Humans ; Immunohistochemistry ; Interstitial collagenase ; Laboratories ; Leukocytes (neutrophilic) ; Macrophages ; Matrilysin ; Matrix metalloproteinase ; Matrix metalloproteinases ; Matrix Metalloproteinases - metabolism ; Medical research ; Medical schools ; Medicine ; Membranes ; Monocytes ; Multiplexing ; Neovascularization, Pathologic - complications ; Neutrophil collagenase ; Neutrophils ; Patients ; Quantitation ; Retinopathy ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - metabolism ; Vitreous Body - enzymology ; Vitreous Body - metabolism</subject><ispartof>PloS one, 2013-12, Vol.8 (12), p.e85857-e85857</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Abu El-Asrar et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Abu El-Asrar et al 2013 Abu El-Asrar et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-5c2ac671349290597609f4fd234d6fec30260ddf31d94320e6bd4068916072993</citedby><cites>FETCH-LOGICAL-c758t-5c2ac671349290597609f4fd234d6fec30260ddf31d94320e6bd4068916072993</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1473341006/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1473341006?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25751,27922,27923,37010,37011,44588,53789,53791,74896</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24392031$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Tsilibary, Effie C</contributor><creatorcontrib>Abu El-Asrar, Ahmed M</creatorcontrib><creatorcontrib>Mohammad, Ghulam</creatorcontrib><creatorcontrib>Nawaz, Mohd Imtiaz</creatorcontrib><creatorcontrib>Siddiquei, Mohammad Mairaj</creatorcontrib><creatorcontrib>Van den Eynde, Kathleen</creatorcontrib><creatorcontrib>Mousa, Ahmed</creatorcontrib><creatorcontrib>De Hertogh, Gert</creatorcontrib><creatorcontrib>Opdenakker, Ghislain</creatorcontrib><title>Relationship between vitreous levels of matrix metalloproteinases and vascular endothelial growth factor in proliferative diabetic retinopathy</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>To investigate which matrix metalloproteinases (MMPs) are more likely to be involved in the angiogenic process in proliferative diabetic retinopathy (PDR), we measured the levels of MMPs in the vitreous fluid from patients with PDR and controls and correlated these levels with the levels of vascular endothelial growth factor (VEGF). Vitreous samples from 32 PDR and 24 nondiabetic patients were studied by mosaic multiplex MMPs enzyme-linked immunosorbent assay (ELISA), single ELISA, Western blot and zymography analysis. Epiretinal membranes from 11 patients with PDR were studied by immunohistochemistry. MMP-8 and MMP-13 were not detected. ELISA, Western blot and gelatin ymography assays revealed significant increases in the expression levels of MMP-1, MMP-7, MMP-9 and VEGF in vitreous samples from PDR patients compared to nondiabetic controls, whereas MMP-2 and MMP-3 were not upregulated in vitreous samples from PDR patients. Significant correlations existed between ELISA and zymography assays for the quantitation of MMP-2 (r=0.407; p=0.039) and MMP-9 (r=0.711; p<0.001). Significant correlations were observed between levels of VEGF and levels of MMP-1 (r=0.845; P<0.001) and MMP-9 (r=0.775; p<0.001), and between levels of MMP-1 and MMP-9 (r=0.857; p<0.001). In epiretinal membranes, cytoplasmic immunoreactivity for MMP-9 was present in vascular endothelial cells and stromal monocytes/macrophages and neutrophils. Our findings suggest that among the MMPs measured, MMP-1 and MMP-9 may contribute to the angiogenic switch in PDR.</description><subject>Analysis</subject><subject>Angiogenesis</subject><subject>Assaying</subject><subject>Cancer</subject><subject>Cell adhesion & migration</subject><subject>Collagenase 3</subject><subject>Consent</subject><subject>Correlation</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetic retinopathy</subject><subject>Diabetic Retinopathy - complications</subject><subject>Diabetic Retinopathy - enzymology</subject><subject>Diabetic Retinopathy - metabolism</subject><subject>Diabetic Retinopathy - pathology</subject><subject>Endothelial cells</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Enzymes</subject><subject>Gelatin</subject><subject>Gelatinase A</subject><subject>Gelatinase B</subject><subject>Hemorrhage</subject><subject>Histology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Interstitial collagenase</subject><subject>Laboratories</subject><subject>Leukocytes (neutrophilic)</subject><subject>Macrophages</subject><subject>Matrilysin</subject><subject>Matrix metalloproteinase</subject><subject>Matrix metalloproteinases</subject><subject>Matrix Metalloproteinases - metabolism</subject><subject>Medical research</subject><subject>Medical schools</subject><subject>Medicine</subject><subject>Membranes</subject><subject>Monocytes</subject><subject>Multiplexing</subject><subject>Neovascularization, Pathologic - complications</subject><subject>Neutrophil collagenase</subject><subject>Neutrophils</subject><subject>Patients</subject><subject>Quantitation</subject><subject>Retinopathy</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>Vitreous Body - enzymology</subject><subject>Vitreous Body - metabolism</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11rHCEUhofS0qRp_0FphUJpL3ar44yON4UQ-rEQCKQft-LqmR0XVzfqbJI_0d9cN9mEbMlFGZwZjs_7Hj16quo1wVNCOfm0DGP0yk3XwcMU467tWv6kOiSC1hNWY_r0wf9B9SKlJcYt7Rh7Xh3UDRUlTA6rP-fgVLbBp8Gu0RzyJYBHG5sjhDEhBxtwCYUerVSO9gqtICvnwjqGDNarBAkpb9BGJT06FRF4E_IAziqHFjFc5gH1SucQkfWoqJztIZaEG0DGqpLPahTL24e1ysP1y-pZr1yCV7vvUfXr65efJ98np2ffZifHpxPN2y5PWl0rzTihjagFbgVnWPRNb2raGNaDprhm2JieEiMaWmNgc9Ng1gnCMK-FoEfV21vftQtJ7kqZJGk4pQ3BmBVidkuYoJZyHe1KxWsZlJU3gRAXUsWyegeSc9LOxZxx06lGMRBUQ1PXutR4jlu-9fq8yzbOV2A0-ByV2zPdn_F2kIuwkbTjnApSDD7sDGK4GCFlubJJg3PKb4-prFtgXgbDBX33D_r47nbUQpUNWN-HkldvTeVxw7moOWm2aaePUOUxsLK63Lvelvie4OOeoDAZrvJCjSnJ2Y_z_2fPfu-z7x-wAyiXhxTceHNx98HmFtQxpBShvy8ywXLbNnfVkNu2kbu2KbI3Dw_oXnTXJ_Qv13YU4A</recordid><startdate>20131231</startdate><enddate>20131231</enddate><creator>Abu El-Asrar, Ahmed M</creator><creator>Mohammad, Ghulam</creator><creator>Nawaz, Mohd Imtiaz</creator><creator>Siddiquei, Mohammad Mairaj</creator><creator>Van den Eynde, Kathleen</creator><creator>Mousa, Ahmed</creator><creator>De Hertogh, Gert</creator><creator>Opdenakker, Ghislain</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131231</creationdate><title>Relationship between vitreous levels of matrix metalloproteinases and vascular endothelial growth factor in proliferative diabetic retinopathy</title><author>Abu El-Asrar, Ahmed M ; Mohammad, Ghulam ; Nawaz, Mohd Imtiaz ; Siddiquei, Mohammad Mairaj ; Van den Eynde, Kathleen ; Mousa, Ahmed ; De Hertogh, Gert ; Opdenakker, Ghislain</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-5c2ac671349290597609f4fd234d6fec30260ddf31d94320e6bd4068916072993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Analysis</topic><topic>Angiogenesis</topic><topic>Assaying</topic><topic>Cancer</topic><topic>Cell adhesion & migration</topic><topic>Collagenase 3</topic><topic>Consent</topic><topic>Correlation</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetic retinopathy</topic><topic>Diabetic Retinopathy - 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Vitreous samples from 32 PDR and 24 nondiabetic patients were studied by mosaic multiplex MMPs enzyme-linked immunosorbent assay (ELISA), single ELISA, Western blot and zymography analysis. Epiretinal membranes from 11 patients with PDR were studied by immunohistochemistry. MMP-8 and MMP-13 were not detected. ELISA, Western blot and gelatin ymography assays revealed significant increases in the expression levels of MMP-1, MMP-7, MMP-9 and VEGF in vitreous samples from PDR patients compared to nondiabetic controls, whereas MMP-2 and MMP-3 were not upregulated in vitreous samples from PDR patients. Significant correlations existed between ELISA and zymography assays for the quantitation of MMP-2 (r=0.407; p=0.039) and MMP-9 (r=0.711; p<0.001). Significant correlations were observed between levels of VEGF and levels of MMP-1 (r=0.845; P<0.001) and MMP-9 (r=0.775; p<0.001), and between levels of MMP-1 and MMP-9 (r=0.857; p<0.001). In epiretinal membranes, cytoplasmic immunoreactivity for MMP-9 was present in vascular endothelial cells and stromal monocytes/macrophages and neutrophils. Our findings suggest that among the MMPs measured, MMP-1 and MMP-9 may contribute to the angiogenic switch in PDR.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24392031</pmid><doi>10.1371/journal.pone.0085857</doi><tpages>e85857</tpages><oa>free_for_read</oa></addata></record> |
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recordid | cdi_plos_journals_1473341006 |
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subjects | Analysis Angiogenesis Assaying Cancer Cell adhesion & migration Collagenase 3 Consent Correlation Diabetes Diabetes mellitus Diabetic retinopathy Diabetic Retinopathy - complications Diabetic Retinopathy - enzymology Diabetic Retinopathy - metabolism Diabetic Retinopathy - pathology Endothelial cells Enzyme-linked immunosorbent assay Enzymes Gelatin Gelatinase A Gelatinase B Hemorrhage Histology Humans Immunohistochemistry Interstitial collagenase Laboratories Leukocytes (neutrophilic) Macrophages Matrilysin Matrix metalloproteinase Matrix metalloproteinases Matrix Metalloproteinases - metabolism Medical research Medical schools Medicine Membranes Monocytes Multiplexing Neovascularization, Pathologic - complications Neutrophil collagenase Neutrophils Patients Quantitation Retinopathy Vascular endothelial growth factor Vascular Endothelial Growth Factor A - metabolism Vitreous Body - enzymology Vitreous Body - metabolism |
title | Relationship between vitreous levels of matrix metalloproteinases and vascular endothelial growth factor in proliferative diabetic retinopathy |
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