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Vasculitis, Atherosclerosis, and Altered HDL Composition in Heme-Oxygenase-1-Knockout Mice

By Kazunobu Ishikawa, Mohamad Navab and Aldons J. Lusis

Abstract

To elucidate roles of heme oxygenase-1 (HO-1) in cardiovascular system, we have analyzed one-year-old HO-1-knockout mice. Homozygous HO-1-knockout mice had severe aortitis and coronary arteritis with mononuclear cellular infiltration and fatty streak formation even on a standard chow diet. Levels of plasma total cholesterol and HDL were similar among the three genotypes. However, homozygous HO-1-knockout mice had lower body weight and plasma triglyceride. HO-1-deficiency resulted in alteration of the composition of HDL. The ratio of apolipoprotein AI to AII in HO-1-knockout mice was reduced about 10-fold as compared to wild-type mice. In addition, paraoxonase, an enzyme against oxidative stress, was reduced less than 50% in HO-1-knockout mice. The knockout mice also exhibited significant elevation of plasma lipid hydroperoxides. This study using aged HO-1-knockout mice strengthened the idea that HO-1 functions to suppress systemic inflammation in artery wall and prevents plasma lipid peroxidation

Topics: Research Article
Publisher: Hindawi Publishing Corporation
OAI identifier: oai:pubmedcentral.nih.gov:3296294
Provided by: PubMed Central
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    1. (1997). A r t o l a ,C .B .C o n d e ,L .B a g a t o l l i
    2. (1999). ApoA1 reduces free cholesterol accumulation in atherosclerotic lesions of apoE-deficient mice transplanted with apoE-expressing macrophages,”
    3. (1993). Atherosclerosis in transgenic mice overexpressing apolipoprotein
    4. (2005). Bilirubin from heme oxygenase-1 attenuates vascular endothelial activation and dysfunction,”
    5. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4,”
    6. (1974). Cobalt induction of hepatic heme oxygenase; with evidence that cytochrome P-450 is not essential for this enzyme activity,”
    7. (1992). Ferritin: a cytoprotective antioxidant strategem of endothelium,”
    8. (1995). Hama etal., “Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein,”
    9. (1997). Heme oxygenase 1 is required for mammalian iron reutilization,”
    10. (1996). Heme oxygenase: a novel target for the modulation of the inflammatoryresponse,”Nature
    11. (2001). Heme oxygenase1 inhibits atherosclerotic lesion formation in LDL-receptor knockout mice,”
    12. (1997). Induction of heme oxygenase-1 inhibits the monocyte transmigration induced by mildly oxidized
    13. (1991). Inhibition of early atherogenesis
    14. (1994). J.H.Qiao,P.Z.Xie,M.C.Fishbeinetal.,“Pathologyofatheromatous lesions in inbred and genetically engineered mice: genetic determination of arterial calcification,”
    15. (1994). J.R.StoneandM.A.Marletta,“Solubleguanylatecyclasefrom bovine lung: activation with nitric oxide and carbon monoxide and spectral characterization of the ferrous and ferric states,”
    16. (1951). L o w r y ,N .J .R o s e b r o u g h ,A .L .F a r r ,a n dR .J .R a n d a l l , “Protein measurement with the Folin phenol reagent,”
    17. (1998). La Du, “Paraoxonase inhibits highdensity lipoprotein oxidation and preserves its functions: a possible peroxidative role for paraoxonase,”
    18. (1991). La Du, “Purification of human serum paraoxonase/arylesterase. Evidence for one esterase catalyzing both activities,”
    19. (1998). Mice lacking serumparaoxonase are susceptible to organophosphate toxicity and atherosclerosis,”
    20. (1996). Native lipoproteins inhibit platelet activation induced by oxidized lipoproteins,”
    21. Paraoxonase prevents accumulation of lipoperoxides in low-density lipoprotein,”FEBSLetters,vol.286,no.1-2,pp.152–154,1991.
    22. (1978). Purification and properties of heme oxygenase from pig spleen microsomes,”
    23. (1987). R.St ock er ,Y .Y amamot o ,A.F .M cDonagh,A.N.Glaz er ,andB . N. Ames, “Bilirubin is an antioxidant of possible physiological importance,”
    24. (1997). Reduced stress defense in heme oxygenase 1-deficient cells,”
    25. (1990). Regulation of ferritin and transferrin receptor mRNAs,”
    26. (1977). Solubilization and partial purification of heme oxygenase from rat liver,”
    27. (2006). t o c k e ra n dM .A .P e r r e l l a ,“ H e m eo x y g e n a s e - 1 :an o v e l drug target for atherosclerotic diseases?”
    28. (1980). The cholesteryl estercycleinmacrophagefoamcells.Continualhydrolysisand re-esterification of cytoplasmic cholesteryl esters,”
    29. (1955). The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum,”
    30. (2009). The role of dysfunctional HDL in atherosclerosis,”

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