Myeloperoxidase and Plasminogen Activator Inhibitor 1 Play a Central Role in Ventricular Remodeling after Myocardial Infarction

Autor: Eric J. Topol, Xiaorong Zhou, Arman T. Askari, Jeanne K. Drinko, Marie Luise Brennan, Annitta Morehead, Marc S. Penn, James D. Thomas, Stanley L. Hazen
Rok vydání: 2003
Předmět:
Time Factors
Myocardial Infarction
030204 cardiovascular system & hematology
Myocardial rupture
Mice
chemistry.chemical_compound
0302 clinical medicine
Leukocytes
Immunology and Allergy
Myocardial infarction
Mice
Knockout
0303 health sciences
Ventricular Remodeling
biology
Survival Rate
medicine.anatomical_structure
Matrix Metalloproteinase 9
Plasminogen activator inhibitor-1
Myeloperoxidase
protease activation
Cardiology
Matrix Metalloproteinase 2
Collagen
medicine.symptom
Oxidation-Reduction
medicine.medical_specialty
Serine Proteinase Inhibitors
Immunology
Inflammation
Article
03 medical and health sciences
Coronary circulation
Coronary Circulation
Internal medicine
Plasminogen Activator Inhibitor 1
medicine
Animals
Humans
Ventricular remodeling
Peroxidase
030304 developmental biology
free radical
chlorination
business.industry
Myocardium
medicine.disease
Enzyme Activation
Mice
Inbred C57BL
chemistry
Heart failure
biology.protein
Leukocyte Common Antigens
business
myocardial rupture
Zdroj: The Journal of Experimental Medicine
ISSN: 1540-9538
0022-1007
DOI: 10.1084/jem.20021426
Popis: 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.
Databáze: OpenAIRE
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