Matrix Metalloproteinase Inhibition Improves Cardiac Dysfunction and Remodeling in 2-Kidney, 1-Clip Hypertension
Abstract Background Enhanced cardiac matrix metalloproteinase activity (MMPs) has been associated with ventricular remodeling and cardiac dysfunction. It is unknown whether MMPs contribute to systolic/diastolic dysfunction and compensatory remodeling in 2-kidney, 1-clip (2K1C) hypertensive rats. To...
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| Veröffentlicht in: | Journal of cardiac failure 2010-07, Vol.16 (7), p.599-608 |
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| creator | Rizzi, Élen, MSc Castro, Michele M., PhD Prado, Cibele M., PhD Silva, Carlos A Fazan, Rubens, MD, PhD Rossi, Marcos A., MD, PhD Tanus-Santos, Jose E., MD, PhD Gerlach, Raquel Fernanda, PhD |
| description | Abstract Background Enhanced cardiac matrix metalloproteinase activity (MMPs) has been associated with ventricular remodeling and cardiac dysfunction. It is unknown whether MMPs contribute to systolic/diastolic dysfunction and compensatory remodeling in 2-kidney, 1-clip (2K1C) hypertensive rats. To test this hypothesis, we used 2K1C rats after 2 weeks of surgery treated or not with a nonspecific inhibitor of MMPs (doxycycline). Methods and Results We found that blood pressure and ±dP/dt increased in 2K1C rats compared with sham groups, and these parameters were attenuated by doxycycline treatment ( P < .05). Doxycycline also reversed cardiac hypertrophy observed in 2K1C rats ( P < .05). Hypertensive rats showed increased MMP-2 levels in zymograms and in the tissue by immunofluorescence ( P < .05) compared with sham groups. Increased total gelatinolytic activity was observed in untreated 2K1C rats when compared with sham groups ( P < .05). Doxycycline decreased total gelatinolytic activity in 2K1C rats to control levels ( P < .05). Conclusion An imbalance in gelatinolytic activity, with increased MMP-2 levels and activity underlies the development of morphological and functional alterations found in the compensatory hypertrophy observed in 2K1C hearts. Because function and structure were restored by doxycycline, the inhibition of MMPs or their modulation may provide beneficial effects for therapeutic intervention in cardiac hypertrophy. |
| doi_str_mv | 10.1016/j.cardfail.2010.02.005 |
| format | Article |
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It is unknown whether MMPs contribute to systolic/diastolic dysfunction and compensatory remodeling in 2-kidney, 1-clip (2K1C) hypertensive rats. To test this hypothesis, we used 2K1C rats after 2 weeks of surgery treated or not with a nonspecific inhibitor of MMPs (doxycycline). Methods and Results We found that blood pressure and ±dP/dt increased in 2K1C rats compared with sham groups, and these parameters were attenuated by doxycycline treatment ( P < .05). Doxycycline also reversed cardiac hypertrophy observed in 2K1C rats ( P < .05). Hypertensive rats showed increased MMP-2 levels in zymograms and in the tissue by immunofluorescence ( P < .05) compared with sham groups. Increased total gelatinolytic activity was observed in untreated 2K1C rats when compared with sham groups ( P < .05). Doxycycline decreased total gelatinolytic activity in 2K1C rats to control levels ( P < .05). Conclusion An imbalance in gelatinolytic activity, with increased MMP-2 levels and activity underlies the development of morphological and functional alterations found in the compensatory hypertrophy observed in 2K1C hearts. Because function and structure were restored by doxycycline, the inhibition of MMPs or their modulation may provide beneficial effects for therapeutic intervention in cardiac hypertrophy.</description><identifier>ISSN: 1071-9164</identifier><identifier>EISSN: 1532-8414</identifier><identifier>DOI: 10.1016/j.cardfail.2010.02.005</identifier><identifier>PMID: 20610236</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; cardiac hypertrophy and hypertension ; Cardiomegaly - drug therapy ; Cardiomegaly - enzymology ; Cardiomegaly - physiopathology ; Cardiovascular ; Doxycycline - pharmacology ; Doxycycline - therapeutic use ; Enzyme Inhibitors - pharmacology ; Enzyme Inhibitors - therapeutic use ; Hypertension, Renovascular - drug therapy ; Hypertension, Renovascular - enzymology ; Hypertension, Renovascular - physiopathology ; Male ; Matrix Metalloproteinase 2 - physiology ; Matrix Metalloproteinase Inhibitors ; MMP-2 ; Rats ; Rats, Wistar ; Surgical Instruments ; Ventricular Remodeling - physiology</subject><ispartof>Journal of cardiac failure, 2010-07, Vol.16 (7), p.599-608</ispartof><rights>Elsevier Inc.</rights><rights>2010 Elsevier Inc.</rights><rights>Copyright 2010 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-491d8c97d352137e03f7fe7d16f852796a2cb337e8b009039a2c159e53253f0b3</citedby><cites>FETCH-LOGICAL-c422t-491d8c97d352137e03f7fe7d16f852796a2cb337e8b009039a2c159e53253f0b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.cardfail.2010.02.005$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20610236$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rizzi, Élen, MSc</creatorcontrib><creatorcontrib>Castro, Michele M., PhD</creatorcontrib><creatorcontrib>Prado, Cibele M., PhD</creatorcontrib><creatorcontrib>Silva, Carlos A</creatorcontrib><creatorcontrib>Fazan, Rubens, MD, PhD</creatorcontrib><creatorcontrib>Rossi, Marcos A., MD, PhD</creatorcontrib><creatorcontrib>Tanus-Santos, Jose E., MD, PhD</creatorcontrib><creatorcontrib>Gerlach, Raquel Fernanda, PhD</creatorcontrib><title>Matrix Metalloproteinase Inhibition Improves Cardiac Dysfunction and Remodeling in 2-Kidney, 1-Clip Hypertension</title><title>Journal of cardiac failure</title><addtitle>J Card Fail</addtitle><description>Abstract Background Enhanced cardiac matrix metalloproteinase activity (MMPs) has been associated with ventricular remodeling and cardiac dysfunction. It is unknown whether MMPs contribute to systolic/diastolic dysfunction and compensatory remodeling in 2-kidney, 1-clip (2K1C) hypertensive rats. To test this hypothesis, we used 2K1C rats after 2 weeks of surgery treated or not with a nonspecific inhibitor of MMPs (doxycycline). Methods and Results We found that blood pressure and ±dP/dt increased in 2K1C rats compared with sham groups, and these parameters were attenuated by doxycycline treatment ( P < .05). Doxycycline also reversed cardiac hypertrophy observed in 2K1C rats ( P < .05). Hypertensive rats showed increased MMP-2 levels in zymograms and in the tissue by immunofluorescence ( P < .05) compared with sham groups. Increased total gelatinolytic activity was observed in untreated 2K1C rats when compared with sham groups ( P < .05). Doxycycline decreased total gelatinolytic activity in 2K1C rats to control levels ( P < .05). Conclusion An imbalance in gelatinolytic activity, with increased MMP-2 levels and activity underlies the development of morphological and functional alterations found in the compensatory hypertrophy observed in 2K1C hearts. Because function and structure were restored by doxycycline, the inhibition of MMPs or their modulation may provide beneficial effects for therapeutic intervention in cardiac hypertrophy.</description><subject>Animals</subject><subject>cardiac hypertrophy and hypertension</subject><subject>Cardiomegaly - drug therapy</subject><subject>Cardiomegaly - enzymology</subject><subject>Cardiomegaly - physiopathology</subject><subject>Cardiovascular</subject><subject>Doxycycline - pharmacology</subject><subject>Doxycycline - therapeutic use</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Enzyme Inhibitors - therapeutic use</subject><subject>Hypertension, Renovascular - drug therapy</subject><subject>Hypertension, Renovascular - enzymology</subject><subject>Hypertension, Renovascular - physiopathology</subject><subject>Male</subject><subject>Matrix Metalloproteinase 2 - physiology</subject><subject>Matrix Metalloproteinase Inhibitors</subject><subject>MMP-2</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Surgical Instruments</subject><subject>Ventricular Remodeling - physiology</subject><issn>1071-9164</issn><issn>1532-8414</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi0Eoh_wFyrfuJBlbCdOckGgBdoVrZD4OFuOPQEvjpPaSUX-PV625cCFk-2Zd-b1PEPIBYMNAyZf7TdGR9tr5zccchD4BqB6RE5ZJXjRlKx8nO9Qs6JlsjwhZyntAaApoX5KTjhIBlzIUzLd6Dm6X_QGZ-39OMVxRhd0QroLP1znZjcGuhty_A4T3WZPpw19t6Z-CeZPUgdLP-MwWvQufKcuUF58dDbg-pKyYuvdRK_WCeOMIWX9M_Kk1z7h8_vznHz78P7r9qq4_nS52769LkzJ-VyULbONaWsrKs5EjSD6usfaMtk3Fa9bqbnpRE40HUALos1vVrWYp69ED504Jy-OffPXbxdMsxpcMui9DjguSdVCyKoqS5aV8qg0cUwpYq-m6AYdV8VAHWCrvXqArQ6wFXCVYefCi3uLpRvQ_i17oJsFb44CzIPeOYwqGYfBoHURzazs6P7v8fqfFiZjdkb7n7hi2o9LDBmjYirlAvXlsPLDxlleNsgGxG_Ygagw</recordid><startdate>20100701</startdate><enddate>20100701</enddate><creator>Rizzi, Élen, MSc</creator><creator>Castro, Michele M., PhD</creator><creator>Prado, Cibele M., PhD</creator><creator>Silva, Carlos A</creator><creator>Fazan, Rubens, MD, PhD</creator><creator>Rossi, Marcos A., MD, PhD</creator><creator>Tanus-Santos, Jose E., MD, PhD</creator><creator>Gerlach, Raquel Fernanda, PhD</creator><general>Elsevier Inc</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>7X8</scope></search><sort><creationdate>20100701</creationdate><title>Matrix Metalloproteinase Inhibition Improves Cardiac Dysfunction and Remodeling in 2-Kidney, 1-Clip Hypertension</title><author>Rizzi, Élen, MSc ; Castro, Michele M., PhD ; Prado, Cibele M., PhD ; Silva, Carlos A ; Fazan, Rubens, MD, PhD ; Rossi, Marcos A., MD, PhD ; Tanus-Santos, Jose E., MD, PhD ; Gerlach, Raquel Fernanda, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-491d8c97d352137e03f7fe7d16f852796a2cb337e8b009039a2c159e53253f0b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>cardiac hypertrophy and hypertension</topic><topic>Cardiomegaly - drug therapy</topic><topic>Cardiomegaly - enzymology</topic><topic>Cardiomegaly - physiopathology</topic><topic>Cardiovascular</topic><topic>Doxycycline - pharmacology</topic><topic>Doxycycline - therapeutic use</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Enzyme Inhibitors - therapeutic use</topic><topic>Hypertension, Renovascular - drug therapy</topic><topic>Hypertension, Renovascular - enzymology</topic><topic>Hypertension, Renovascular - physiopathology</topic><topic>Male</topic><topic>Matrix Metalloproteinase 2 - physiology</topic><topic>Matrix Metalloproteinase Inhibitors</topic><topic>MMP-2</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Surgical Instruments</topic><topic>Ventricular Remodeling - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rizzi, Élen, MSc</creatorcontrib><creatorcontrib>Castro, Michele M., PhD</creatorcontrib><creatorcontrib>Prado, Cibele M., PhD</creatorcontrib><creatorcontrib>Silva, Carlos A</creatorcontrib><creatorcontrib>Fazan, Rubens, MD, PhD</creatorcontrib><creatorcontrib>Rossi, Marcos A., MD, PhD</creatorcontrib><creatorcontrib>Tanus-Santos, Jose E., MD, PhD</creatorcontrib><creatorcontrib>Gerlach, Raquel Fernanda, PhD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cardiac failure</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rizzi, Élen, MSc</au><au>Castro, Michele M., PhD</au><au>Prado, Cibele M., PhD</au><au>Silva, Carlos A</au><au>Fazan, Rubens, MD, PhD</au><au>Rossi, Marcos A., MD, PhD</au><au>Tanus-Santos, Jose E., MD, PhD</au><au>Gerlach, Raquel Fernanda, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Matrix Metalloproteinase Inhibition Improves Cardiac Dysfunction and Remodeling in 2-Kidney, 1-Clip Hypertension</atitle><jtitle>Journal of cardiac failure</jtitle><addtitle>J Card Fail</addtitle><date>2010-07-01</date><risdate>2010</risdate><volume>16</volume><issue>7</issue><spage>599</spage><epage>608</epage><pages>599-608</pages><issn>1071-9164</issn><eissn>1532-8414</eissn><abstract>Abstract Background Enhanced cardiac matrix metalloproteinase activity (MMPs) has been associated with ventricular remodeling and cardiac dysfunction. It is unknown whether MMPs contribute to systolic/diastolic dysfunction and compensatory remodeling in 2-kidney, 1-clip (2K1C) hypertensive rats. To test this hypothesis, we used 2K1C rats after 2 weeks of surgery treated or not with a nonspecific inhibitor of MMPs (doxycycline). Methods and Results We found that blood pressure and ±dP/dt increased in 2K1C rats compared with sham groups, and these parameters were attenuated by doxycycline treatment ( P < .05). Doxycycline also reversed cardiac hypertrophy observed in 2K1C rats ( P < .05). Hypertensive rats showed increased MMP-2 levels in zymograms and in the tissue by immunofluorescence ( P < .05) compared with sham groups. Increased total gelatinolytic activity was observed in untreated 2K1C rats when compared with sham groups ( P < .05). Doxycycline decreased total gelatinolytic activity in 2K1C rats to control levels ( P < .05). Conclusion An imbalance in gelatinolytic activity, with increased MMP-2 levels and activity underlies the development of morphological and functional alterations found in the compensatory hypertrophy observed in 2K1C hearts. Because function and structure were restored by doxycycline, the inhibition of MMPs or their modulation may provide beneficial effects for therapeutic intervention in cardiac hypertrophy.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>20610236</pmid><doi>10.1016/j.cardfail.2010.02.005</doi><tpages>10</tpages></addata></record> |
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| subjects | Animals cardiac hypertrophy and hypertension Cardiomegaly - drug therapy Cardiomegaly - enzymology Cardiomegaly - physiopathology Cardiovascular Doxycycline - pharmacology Doxycycline - therapeutic use Enzyme Inhibitors - pharmacology Enzyme Inhibitors - therapeutic use Hypertension, Renovascular - drug therapy Hypertension, Renovascular - enzymology Hypertension, Renovascular - physiopathology Male Matrix Metalloproteinase 2 - physiology Matrix Metalloproteinase Inhibitors MMP-2 Rats Rats, Wistar Surgical Instruments Ventricular Remodeling - physiology |
| title | Matrix Metalloproteinase Inhibition Improves Cardiac Dysfunction and Remodeling in 2-Kidney, 1-Clip Hypertension |
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