Abstract
Objective
Animal models of atherosclerosis are essential to elucidate disease mechanisms and
develop new therapies. Each model features advantages and disadvantages in exemplifying
the pathophysiology of human atherosclerosis. Diet-induced development of atherosclerosis
in Octodon degus (degu) was examined to demonstrate the potential of the degu as a model of human
atherosclerosis.
Methods
Degus were fed for 16 weeks with either normal chow or chow containing 0.25% cholesterol
and 6% palm oil to induce atherosclerosis. The lipid compositions of plasma lipoproteins
and aortas were determined. Locations of aortic lesions were mapped by imaging of
fluorescently stained aortic lesions. Lesion morphology in the brachiocephalic artery
was detected by histological staining.
Results
Total plasma cholesterol in chow-fed degus was distributed approximately 60% in HDL,
30% in LDL and less than 10% in VLDL. Cholesterol-fed degus exhibited 4- to 5-fold
increases in total plasma cholesterol, principally in the VLDL and LDL fractions.
Cholesteryl ester transfer protein activity of similar magnitude to that in human
plasma was detected in chow-fed degu plasma. Cholesterol-fed degus developed cholesteryl
ester-rich atherosclerotic lesions throughout the aorta. Histological examination
of lesions in the brachiocephalic artery showed well-formed, foam cell-rich lesions
populated with inflammatory cells. It is also noteworthy that all the degus in this
study exhibited hyperglycemia.
Conclusion
These results demonstrate that degus have a human-like lipoprotein metabolism and
develop extensive atherosclerosis with cholesterol feeding in the presence of hyperglycemia.
These features, combined with the manageable size and handling characteristics, point
to the potential of the degu as a useful model for atherosclerosis research.
Keywords
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Article info
Publication history
Published online: July 15, 2010
Accepted:
June 1,
2010
Received in revised form:
April 30,
2010
Received:
January 18,
2010
Identification
Copyright
© 2010 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.