title: Inhibition of collar-induced carotid atherosclerosis by recombinant apoA-I cysteine mutants in apoE-deficient mice.
abstract: The previous studies in our laboratory revealed that seven cysteine mutants of apolipoprotein A-I (apoA-I) have different structural features and biological activities in vitro and in vivo. To investigate the potential cardioprotective effects of apolipoprotein A-I(N74C) [apoA-I(N74C)], we examined the anti-inflammatory, antioxidant, and antiatherosclerotic effects of this cysteine mutant in a rapid atherosclerosis model induced by perivascular carotid collar placement in apoE⁻/⁻ mice. Lipid-free apoA-I(N74C) showed a significant increased antioxidant potency in low density lipoprotein (LDL) oxidation in vitro and reduced intracellular lipid accumulation in THP-1-derived macrophages, relative to wild-type apoA-I (apoA-Iwt). Mice injected with recombinant HDL (rHDL) reconstituted with apoA-I(N74C) (named rHDL74) through tail veins (40 mg/kg of body weight, three injections) had a significant lower level of serum interleukin-6 (IL-6) and enhanced serum antioxidation compared with mice receiving rHDL reconstituted with apoA-Iwt (named rHDLwt). Moreover, compared with rHDLwt, the rHDL74 in vivo injection resulted in a significant decrease in plaque size, ratio of aorta intima to media, arterial remodeling, and macrophage content in lesions. In summary, intravenous injection with rHDL74 reconstituted with apoA-I cysteine mutant apoA-I (N74C) dramatically delays the development of atherosclerosis induced by perivascular carotid collar placement and reduces vascular remodeling in the carotid artery in apoE⁻/⁻ mice.
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xinbo
authors.initials: X
authors.lastname: Zhang
authors.forename: Xuewei
authors.initials: X
authors.lastname: Zhu
authors.forename: Baosheng
authors.initials: B
authors.lastname: Chen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D016632:Apolipoprotein A-I / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism*; D002340:Carotid Artery Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D010084:Oxidation-Reduction / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D016207:Cytokines; D015850:Interleukin-6; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011994:Recombinant Proteins
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