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Atherosclerosis: visualising oxidised LDL in zebrafish

Journal
Disease Models & Mechanisms
1754-8403
Publisher
The Company of Biologists
Publication Date
Keywords
  • Research Highlights
Disciplines
  • Biology
  • Medicine

Abstract

Oxidation of low-density lipoprotein (LDL; the main vehicle for ‘bad’ cholesterol) is thought to contribute to the pathology of atherosclerosis in part by acting as a pro-inflammatory component of plaques. Antibodies specific for oxidised LDL (ox-LDL) have been used to visualise atherosclerotic lesions in mice and, when applied as a treatment, lessened signs of the disease through inhibiting the uptake of ox-LDL by macrophages. Fang et al. now apply these principles in zebrafish to develop an efficient system for testing new atherosclerosis therapies. Previously, the authors showed that zebrafish that were fed a high-cholesterol diet (HCD) exhibited pathological processes resembling early atherosclerosis in humans. In their new paper, they expressed an inducible and fluorescently labelled form of IK17, a monoclonal antibody specific for ox-LDL, in HCD-fed zebrafish to enable visualisation of ox-LDL in vivo. Vascular accumulation of ox-LDL decreased when HCD-fed zebrafish were switched to a normal diet, or following exposure to probucol, a potent antioxidant. Constitutive IK17 expression impaired ox-LDL binding by macrophages and markedly inhibited vascular ox-LDL accumulation in vivo. These data suggest that early treatment with ox-LDL-specific antibodies might be a viable therapy in humans with the disease. FangL.GreenS. R.BaekJ. S.LeeS. H.EllettF.DeerE.LieschkeG. J.WitztumJ. L.TsimikasS.MillerY. I. ( 2011). In vivo visualization and attenuation of oxidized lipid accumulation in hypercholesterolemic zebrafish. J. Clin. Invest. [Epub ahead of print] doi: 10.1172/JCI57755

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