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Published on: September 26, 2018
Increased atherosclerosis in myeloperoxidase-deficient mice
M L Brennan1, M M Anderson, D M Shih
1Department of Microbiology, Immunology and Molecular Genetics, University of California-Los Angeles (UCLA), Los Angeles, California, USA.
The Journal of Clinical Investigation
|February 22, 2001
Summary
Myeloperoxidase (MPO) deficiency unexpectedly worsened atherosclerosis in mice, suggesting MPO may protect against this disease. This contrasts with findings in human atherosclerosis, highlighting species-specific roles.
Area of Science:
- Biochemistry
- Immunology
- Cardiovascular Research
Background:
- Myeloperoxidase (MPO) is an enzyme produced by phagocytes, generating oxidants involved in host defense and tissue damage.
- MPO and its products are found in human atherosclerotic plaques, suggesting a role in artery wall modification.
Purpose of the Study:
- To investigate the role of MPO in atherosclerosis using MPO-deficient mice.
- To compare MPO's role in murine and human atherosclerosis.
Main Methods:
- Generated MPO-deficient mice and assessed their neutrophil function in vitro and in vivo.
- Utilized a mouse model of atherosclerosis by repopulating LDL receptor-deficient mice with MPO-deficient or wild-type bone marrow.
- Analyzed aortic lesions for size and chlorotyrosine content.
Main Results:
- MPO-deficient neutrophils lacked peroxidase and chlorination activity and failed to kill Candida albicans.
- MPO-deficient mice exhibited approximately 50% larger atherosclerotic lesions compared to controls.
- Chlorotyrosine, a marker of MPO activity, was undetectable in murine aortic lesions, unlike in human plaques.
Conclusions:
- MPO-generated reactive intermediates appear to play a protective role in murine atherosclerosis.
- Significant differences exist between MPO's role in mouse and human atherosclerosis, particularly concerning protein oxidation.
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