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Hypochlorite-modified (lipo)proteins are present in rabbit lesions in response to dietary cholesterol
1Institute of Medical Biochemistry and Molecular Biology, Karl-Franzens University, Graz, A-8010, Austria. ernst.malle@kfunigraz.ac.at
Abstract:
Myeloperoxidase (MPO), a heme enzyme secreted by activated phagocytes, generates an array of oxidants proposed to play critical roles in host defense, tissues damage, and foam cell formation. Although neutrophils are the major source for MPO, the enzyme could be identified abundantly in circulating monocytes and monocytes/macrophages in rabbit lesions. MPO is the only enzyme known to generate hypochlorous acid (HOCl) and HOCl-modified lipoproteins have pronounced atherogenic and/or proinflammatory features in vivo and in vitro. Using specific monoclonal antibodies, HOCl-modified (lipo)proteins were detected in atherosclerotic plaques of heterozygous Watanabe heritable hyperlipidemic rabbits and to a lesser extent in a specific strain of New Zealand White rabbits with a high atherosclerotic response to hypercholesterolemia. Colocalization of immunoreactive MPO and HOCl-modified-epitopes in serial sections of rabbit lesions provides convincing evidence for MPO-H2O2-chloride system-mediated oxidation of (lipo)proteins under in vivo conditions. We propose that monocyte-derived MPO could connect chronic inflammatory conditions with arterial lipid/lipoprotein deposition during diet-induced atherogenesis in rabbits.
Insights
Myeloperoxidase (MPO) generates oxidants that promote atherosclerosis. Monocyte-derived MPO links inflammation to arterial lipid deposition in rabbits, highlighting its role in atherogenesis.
Area of Science:
- Biochemistry
- Immunology
- Cardiovascular Research
Background:
- Myeloperoxidase (MPO) is a heme enzyme secreted by phagocytes, crucial for host defense and implicated in tissue damage and foam cell formation.
- While neutrophils are the primary source, MPO is also found in monocytes and macrophages within atherosclerotic lesions.
- MPO generates hypochlorous acid (HOCl), which modifies lipoproteins, enhancing their atherogenic and proinflammatory properties.
Purpose of the Study:
- To investigate the role of myeloperoxidase (MPO) in the development of atherosclerosis.
- To determine if MPO-derived oxidants contribute to the modification of lipoproteins in vivo within atherosclerotic plaques.
- To explore the connection between monocyte-derived MPO, inflammation, and lipid deposition in diet-induced atherogenesis.
Main Methods:
- Detection of HOCl-modified (lipo)proteins using specific monoclonal antibodies in atherosclerotic rabbit models.
- Analysis of MPO and HOCl-modified epitope colocalization in serial sections of rabbit arterial lesions.
- Utilizing Watanabe heritable hyperlipidemic rabbits and a hypercholesterolemia-prone rabbit strain.
Main Results:
- HOCl-modified (lipo)proteins were detected in atherosclerotic plaques of hyperlipidemic rabbits.
- Colocalization of MPO and HOCl-modified epitopes confirmed MPO-mediated oxidation of (lipo)proteins in vivo.
- Evidence suggests monocyte-derived MPO plays a role in linking inflammation to arterial lipid deposition.
Conclusions:
- Monocyte-derived MPO is implicated in the oxidation of lipoproteins within atherosclerotic lesions.
- The MPO-H2O2-chloride system contributes to in vivo (lipo)protein oxidation during atherogenesis.
- MPO may serve as a critical link between chronic inflammation and arterial lipid accumulation in diet-induced atherosclerosis.