Myeloperoxidase and plasminogen activator inhibitor 1 play a central role in ventricular remodeling after myocardial infarction
Left ventricular (LV) remodeling after myocardial infarction (MI) results in LV dilation, a major cause of congestive heart failure and sudden cardiac death. Ischemic injury and the ensuing inflammatory response participate in LV remodeling, leading to myocardial rupture and LV dilation. Myeloperoxi...
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| Veröffentlicht in: | The Journal of experimental medicine 2003-03, Vol.197 (5), p.615-624 |
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| creator | Askari, Arman T Brennan, Marie-Luise Zhou, Xiaorong Drinko, Jeanne Morehead, Annitta Thomas, James D Topol, Eric J Hazen, Stanley L Penn, Marc S |
| description | Left ventricular (LV) remodeling after myocardial infarction (MI) results in LV dilation, a major cause of congestive heart failure and sudden cardiac death. Ischemic injury and the ensuing inflammatory response participate in LV remodeling, leading to myocardial rupture and LV dilation. Myeloperoxidase (MPO), which accumulates in the infarct zone, is released from neutrophils and monocytes leading to the formation of reactive chlorinating species capable of oxidizing proteins and altering biological function. We studied acute myocardial infarction (AMI) in a chronic coronary artery ligation model in MPO null mice (MPO(-/-)). MPO(-/-) demonstrated decreased leukocyte infiltration, significant reduction in LV dilation, and marked preservation of LV function. The mechanism appears to be due to decreased oxidative inactivation of plasminogen activator inhibitor 1 (PAI-1) in the MPO(-/-), leading to decreased tissue plasmin activity. MPO and PAI-1 are shown to have a critical role in the LV response immediately after MI, as demonstrated by markedly delayed myocardial rupture in the MPO(-/-) and accelerated rupture in the PAI-1(-/-). These data offer a mechanistic link between inflammation and LV remodeling by demonstrating a heretofore unrecognized role for MPO and PAI-1 in orchestrating the myocardial response to AMI. |
| doi_str_mv | 10.1084/jem.20021426 |
| format | Article |
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Ischemic injury and the ensuing inflammatory response participate in LV remodeling, leading to myocardial rupture and LV dilation. Myeloperoxidase (MPO), which accumulates in the infarct zone, is released from neutrophils and monocytes leading to the formation of reactive chlorinating species capable of oxidizing proteins and altering biological function. We studied acute myocardial infarction (AMI) in a chronic coronary artery ligation model in MPO null mice (MPO(-/-)). MPO(-/-) demonstrated decreased leukocyte infiltration, significant reduction in LV dilation, and marked preservation of LV function. The mechanism appears to be due to decreased oxidative inactivation of plasminogen activator inhibitor 1 (PAI-1) in the MPO(-/-), leading to decreased tissue plasmin activity. MPO and PAI-1 are shown to have a critical role in the LV response immediately after MI, as demonstrated by markedly delayed myocardial rupture in the MPO(-/-) and accelerated rupture in the PAI-1(-/-). 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Ischemic injury and the ensuing inflammatory response participate in LV remodeling, leading to myocardial rupture and LV dilation. Myeloperoxidase (MPO), which accumulates in the infarct zone, is released from neutrophils and monocytes leading to the formation of reactive chlorinating species capable of oxidizing proteins and altering biological function. We studied acute myocardial infarction (AMI) in a chronic coronary artery ligation model in MPO null mice (MPO(-/-)). MPO(-/-) demonstrated decreased leukocyte infiltration, significant reduction in LV dilation, and marked preservation of LV function. The mechanism appears to be due to decreased oxidative inactivation of plasminogen activator inhibitor 1 (PAI-1) in the MPO(-/-), leading to decreased tissue plasmin activity. MPO and PAI-1 are shown to have a critical role in the LV response immediately after MI, as demonstrated by markedly delayed myocardial rupture in the MPO(-/-) and accelerated rupture in the PAI-1(-/-). These data offer a mechanistic link between inflammation and LV remodeling by demonstrating a heretofore unrecognized role for MPO and PAI-1 in orchestrating the myocardial response to AMI.</description><subject>Animals</subject><subject>Collagen - metabolism</subject><subject>Coronary Circulation</subject><subject>Enzyme Activation</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Leukocyte Common Antigens - metabolism</subject><subject>Leukocytes - metabolism</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Matrix Metalloproteinase 9 - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Myocardial Infarction - metabolism</subject><subject>Myocardium - cytology</subject><subject>Myocardium - metabolism</subject><subject>Myocardium - pathology</subject><subject>Oxidation-Reduction</subject><subject>Peroxidase - genetics</subject><subject>Peroxidase - metabolism</subject><subject>Plasminogen Activator Inhibitor 1 - metabolism</subject><subject>Serine Proteinase Inhibitors - metabolism</subject><subject>Survival Rate</subject><subject>Time Factors</subject><subject>Ventricular Remodeling</subject><issn>0022-1007</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkTtvFDEUhS0EIptAR41cUWUSv8aeaZBQFAhSIhqorTue640jj73Ys6tsxV9nVlleFdV9fTo6V4eQN5xdcNapywecLgRjgiuhn5EVbxVr-lZ2z8lq2YqGM2ZOyGmtD4xxpVr9kpxwoXnbM7EiP-72GPMGS34MI1SkkEa6iVCnkPIaEwU3hx3MudCQ7sMQDh0_EHsK1GGaC0RacsTlTneHObhthEILTnnEGNKagp-x0GmfHZQxLHxIHsoinNMr8sJDrPj6WM_It4_XX69umtsvnz5ffbhtnDJmbqA3RgnlkKMfpDQ4DNrpfmR-aEVnQBvmJR9aprSQEoQ0pmeowXnfaVQgz8j7J93NdphwPBq3mxImKHubIdh_Lync23XeWcF72Um-CLw7CpT8fYt1tlOoDmOEhHlbrZHMsE7r_4K8M22vjFzA8yfQlVxrQf_bDWf2EK1dorW_ol3wt39_8Ac-Zil_Arx-o2o</recordid><startdate>20030303</startdate><enddate>20030303</enddate><creator>Askari, Arman T</creator><creator>Brennan, Marie-Luise</creator><creator>Zhou, Xiaorong</creator><creator>Drinko, Jeanne</creator><creator>Morehead, Annitta</creator><creator>Thomas, James D</creator><creator>Topol, Eric J</creator><creator>Hazen, Stanley L</creator><creator>Penn, Marc S</creator><general>The Rockefeller University Press</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>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20030303</creationdate><title>Myeloperoxidase and plasminogen activator inhibitor 1 play a central role in ventricular remodeling after myocardial infarction</title><author>Askari, Arman T ; Brennan, Marie-Luise ; Zhou, Xiaorong ; Drinko, Jeanne ; Morehead, Annitta ; Thomas, James D ; Topol, Eric J ; Hazen, Stanley L ; Penn, Marc S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c477t-a977424ce1efb337ebb6c69d0fb5287a670f31b5046233a237790e6acff86e4a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Collagen - metabolism</topic><topic>Coronary Circulation</topic><topic>Enzyme Activation</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Leukocyte Common Antigens - metabolism</topic><topic>Leukocytes - metabolism</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Matrix Metalloproteinase 9 - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Myocardial Infarction - metabolism</topic><topic>Myocardium - cytology</topic><topic>Myocardium - metabolism</topic><topic>Myocardium - pathology</topic><topic>Oxidation-Reduction</topic><topic>Peroxidase - genetics</topic><topic>Peroxidase - metabolism</topic><topic>Plasminogen Activator Inhibitor 1 - metabolism</topic><topic>Serine Proteinase Inhibitors - metabolism</topic><topic>Survival Rate</topic><topic>Time Factors</topic><topic>Ventricular Remodeling</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Askari, Arman T</creatorcontrib><creatorcontrib>Brennan, Marie-Luise</creatorcontrib><creatorcontrib>Zhou, Xiaorong</creatorcontrib><creatorcontrib>Drinko, Jeanne</creatorcontrib><creatorcontrib>Morehead, Annitta</creatorcontrib><creatorcontrib>Thomas, James D</creatorcontrib><creatorcontrib>Topol, Eric J</creatorcontrib><creatorcontrib>Hazen, Stanley L</creatorcontrib><creatorcontrib>Penn, Marc S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of experimental medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Askari, Arman T</au><au>Brennan, Marie-Luise</au><au>Zhou, Xiaorong</au><au>Drinko, Jeanne</au><au>Morehead, Annitta</au><au>Thomas, James D</au><au>Topol, Eric J</au><au>Hazen, Stanley L</au><au>Penn, Marc S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Myeloperoxidase and plasminogen activator inhibitor 1 play a central role in ventricular remodeling after myocardial infarction</atitle><jtitle>The Journal of experimental medicine</jtitle><addtitle>J Exp Med</addtitle><date>2003-03-03</date><risdate>2003</risdate><volume>197</volume><issue>5</issue><spage>615</spage><epage>624</epage><pages>615-624</pages><issn>0022-1007</issn><eissn>1540-9538</eissn><abstract>Left ventricular (LV) remodeling after myocardial infarction (MI) results in LV dilation, a major cause of congestive heart failure and sudden cardiac death. Ischemic injury and the ensuing inflammatory response participate in LV remodeling, leading to myocardial rupture and LV dilation. Myeloperoxidase (MPO), which accumulates in the infarct zone, is released from neutrophils and monocytes leading to the formation of reactive chlorinating species capable of oxidizing proteins and altering biological function. We studied acute myocardial infarction (AMI) in a chronic coronary artery ligation model in MPO null mice (MPO(-/-)). MPO(-/-) demonstrated decreased leukocyte infiltration, significant reduction in LV dilation, and marked preservation of LV function. The mechanism appears to be due to decreased oxidative inactivation of plasminogen activator inhibitor 1 (PAI-1) in the MPO(-/-), leading to decreased tissue plasmin activity. MPO and PAI-1 are shown to have a critical role in the LV response immediately after MI, as demonstrated by markedly delayed myocardial rupture in the MPO(-/-) and accelerated rupture in the PAI-1(-/-). These data offer a mechanistic link between inflammation and LV remodeling by demonstrating a heretofore unrecognized role for MPO and PAI-1 in orchestrating the myocardial response to AMI.</abstract><cop>United States</cop><pub>The Rockefeller University Press</pub><pmid>12615902</pmid><doi>10.1084/jem.20021426</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Collagen - metabolism Coronary Circulation Enzyme Activation Humans Inflammation Leukocyte Common Antigens - metabolism Leukocytes - metabolism Matrix Metalloproteinase 2 - metabolism Matrix Metalloproteinase 9 - metabolism Mice Mice, Inbred C57BL Mice, Knockout Myocardial Infarction - metabolism Myocardium - cytology Myocardium - metabolism Myocardium - pathology Oxidation-Reduction Peroxidase - genetics Peroxidase - metabolism Plasminogen Activator Inhibitor 1 - metabolism Serine Proteinase Inhibitors - metabolism Survival Rate Time Factors Ventricular Remodeling |
| title | Myeloperoxidase and plasminogen activator inhibitor 1 play a central role in ventricular remodeling after myocardial infarction |
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