Atherosclerosis in Octodon degus (degu) as a model for human disease.
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.


CONCLUSIONS
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.
Homan
Reynold
R
AlphaCore Pharma, 333 Parkland Plaza, Suite 5, Ann Arbor, MI, USA. reyn.homan@alphacorepharma.com
Hanselman
Jeffrey C
JC
Bak-Mueller
Sandra
S
Washburn
Michelle
M
Lester
Patrick
P
Jensen
Heather E
HE
Pinkosky
Stephen L
SL
Castle
Christine
C
Taylor
Bruce
B
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000097:blood / Q000209:etiology / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D016122:Brachiocephalic Trunk / Q000378:metabolism / Q000473:pathology; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood; D002791:Cholesterol, Dietary / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000209:etiology; D008297:Male; D046329:Octodon; D000073878:Palm Oil; D010938:Plant Oils; D013997:Time Factors
D015415:Biomarkers; D001786:Blood Glucose; D053480:Cholesterol Ester Transfer Proteins; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D010938:Plant Oils; D000073878:Palm Oil