Lipid and lipoprotein metabolism in zebrafish and in humans are remarkably similar.
Zebrafish express all major nuclear receptors, lipid transporters, apolipoproteins
and enzymes involved in lipoprotein metabolism. Unlike mice, zebrafish express cetp and the Cetp activity is detected in zebrafish plasma. Feeding zebrafish a high cholesterol
diet, without any genetic intervention, results in significant hypercholesterolemia
and robust lipoprotein oxidation, making zebrafish an attractive animal model to study
mechanisms relevant to early development of human atherosclerosis. These studies are
facilitated by the optical transparency of zebrafish larvae and the availability of
transgenic zebrafish expressing fluorescent proteins in endothelial cells and macrophages.
Thus, vascular processes can be monitored in live animals. In this review article,
we discuss recent advances in using dyslipidemic zebrafish in atherosclerosis-related
studies. We also summarize recent work connecting lipid metabolism with regulation
of angiogenesis, the work that considerably benefited from using the zebrafish model.
These studies uncovered the role of aibp, abca1, abcg1, mtp, apoB, and apoC2 in regulation of angiogenesis in zebrafish and paved the way for future studies in
mammals, which may suggest new therapeutic approaches to modulation of excessive or
diminished angiogenesis contributing to the pathogenesis of human disease.
Abbreviations:
AIBP (apoA-I binding protein), CE (cholesterol ester), CETP (cholesterol ester transfer protein), DsRed (red fluorescent protein from Discosoma sp.), EC (endothelial cells), EGFP (enhanced green fluorescent protein), HCD (high cholesterol diet), HDL (high-density lipoprotein), LDL (low-density lipoprotein), LPL (lipoprotein lipase), MDA (malondialdehyde), OxCE (oxidized CE), OxPC (oxidized phosphatidylcholine), PLA2 (phospholipase A2), SeA (segmental artery), SIV (subintestinal vein), VLDL (very low-density lipoprotein)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: October 04, 2013
Accepted:
September 10,
2013
Received in revised form:
September 7,
2013
Received:
July 8,
2013
Footnotes
Conflict of interest: None.
Work in the authors' laboratory is supported by the NIH grants HL093767 (Y.I.M.), HL055798 (Y.I.M.) and HL114734 (L.F.). All authors have read the journal's policy on conflicts of interest and wish to disclose that Y.M. has received an investigator-initiated grant from Merck and is a co-inventor of a patent owned by the University of California for the use of the hypercholesterolemic zebrafish model. Y.M. and L.F. are co-inventors of a patent owned by the University of California related to therapeutic applications of apoA-I binding protein.
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