title: Alpha-tocopherol and astaxanthin decrease macrophage infiltration, apoptosis and vulnerability in atheroma of hyperlipidaemic rabbits.
abstract: The composition of atherosclerotic plaques, not just macroscopical lesion size, has been implicated in their susceptibility to rupture and the risk of thrombus formation. By focusing on the quality of lipids, macrophages, apoptosis, collagen, metalloproteinase expression and plaque integrity, we evaluated the possible anti-atherosclerotic effect of the antioxidants alpha-tocopherol and astaxanthin in Watanabe heritable hyperlipidemic (WHHL) rabbits. Thirty-one WHHL rabbits were divided into three groups and were fed a standard diet, as controls (N =10), or a standard diet with the addition of 500 mg alpha-tocopherol per kg feed (N =11) or 100 mg astaxanthin per kg feed (N =10) for 24 weeks. We found that both antioxidants, particularly astaxanthin, significantly decreased macrophage infiltration in the plaques although they did not affect lipid accumulation. All lesions in the astaxanthin-treated rabbits were classified as early plaques according to the distribution of collagen and smooth muscle cells. Both antioxidants also improved plaque stability and significantly diminished apoptosis, which mainly occurred in macrophages, matrix metalloproteinase three expressions and plaque ruptures. Although neither antioxidant altered the positive correlations between the lesion size and lipid accumulation, the lesion size and apoptosis were only positively correlated in the control group. Astaxanthin and alpha-tocopherol may improve plaque stability by decreasing macrophage infiltration and apoptosis in this atherosclerotic setting. Apoptosis reduction by alpha-tocopherol and astaxanthin may be a new anti-atherogenic property of these antioxidants.
authors.affiliation: Division of Pathology-II, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden. weilli@inr.liu.se
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Anna
authors.initials: A
authors.lastname: Hellsten
authors.forename: Leif S
authors.initials: LS
authors.lastname: Jacobsson
authors.forename: Henrik M
authors.initials: HM
authors.lastname: Blomqvist
authors.forename: Anders G
authors.initials: AG
authors.lastname: Olsson
authors.forename: Xi-Ming
authors.initials: XM
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001013:Aorta, Thoracic / Q000737:chemistry / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D001161:Arteriosclerosis / Q000473:pathology / Q000517:prevention & control*; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D006949:Hyperlipidemias / Q000188:drug therapy*; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000032:analysis; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D019278:Matrix Metalloproteinase 3 / Q000032:analysis / Q000378:metabolism; D011817:Rabbits; D024341:Xanthophylls; D024502:alpha-Tocopherol / Q000494:pharmacology / Q000627:therapeutic use*; D019207:beta Carotene / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D008055:Lipids; D024341:Xanthophylls; D019207:beta Carotene; C005948:astaxanthine; D003094:Collagen; D019278:Matrix Metalloproteinase 3; D024502:alpha-Tocopherol