Atherosclerosis
Diet- Induced Atherosclerosis/Hypercholesterolemiain Rodent Models

ReportIn the past, Western-type diets have been made by adding highlevels of fat and cholesterol to grain-based chow diets. The additionof ingredients to chows can dilute other nutrients (i.e. vitamins,
minerals, protein, etc) and non-nutrients (i.e. phytoestrogens), so
their use in atherosclerosis research has been criticized (5). In order
to avoid this issue, purified ingredient diet formulas which are open
to the public (i.e. AIN-76A) can be easily revised to intentionallyalter the atherosclerosis phenotype by adding in fat calories (i.e. dairy
butter, hydrogenated coconut oil) in place of purified carbohydrate
calories only (i.e. sucrose, corn starch). This method of modification
maintains nutrient to calorie ratios, which is important as animals
typically eat for calories, not weight of food. Furthermore,casein-based purified diets contain no phytoestrogens (or otherphytochemicals) unlike typical grain-based chows which can havehighly variable levels (6). Since the presence of phytoestrogencontaining sources (i.e. soy protein and isolated isoflavones) has
been found to influence atherosclerosis and lipoprotein metabolism
in various rodent models (7-13), the use of purified Western-type
diets provides a clean ‘reagent’ for inducing this disease. That being
said, not all rodent models respond the same to a given Western-type
purified diet due to genetic differences. This review will highlightcommonly used dietary factors able to influence LDL-C andatherosclerosis in various rodent models, as well as some of thepotential benefits and drawbacks associated with using thesemodels for disease induction.

Wild Type Mice and Rats
Wild type mice, such as the C57BL/6 mouse, are relatively resistant toatherosclerosis, but have the capacity to develop mild atherosclerosis
under certain conditions. Unlike humans, they typically have a very
low proportion of TC as LDL-C, and most cholesterol in circulation

ReviseDiet 1

Diet 1 = D12102 (10 kcal% Fat,
0% Cholesterol, 0% Cholic Acid)

Diet 2

Diet 2 = D12107 (40 kcal% Fat,
0.5% Cholesterol, 0% Cholic Acid)

Diet 3

Diet 3 = D12108 (40 kcal% Fat,
1.25% Cholesterol, 0% Cholic Acid)

Brief Scientific Literature Review- October 2008by Michael A. Pellizzon, Ph.D. Senior Scientist, Research Diets, Inc.

Atherosclerosis is a complex chronic disease characterized by theaccumulation of lipids within arterial walls that eventually go on
to form plaques, which can cause narrowing, hardening, and/or
complete blockage of arteries. One well known risk factor in humans
is hypercholesterolemia (i.e. elevated total cholesterol (TC) andlow-density lipoprotein cholesterol (LDL-C)) (1), and other important
contributors to this disease include inflammation, oxidative stress,
and insulin resistance (2, 3). Foods high in dietary saturated fat (SF)and cholesterol (i.e. “Western-type diets”) have been linked toelevations in circulating cholesterol levels (in particular, LDL-C) (4),prompting the recommendation that humans limit the intake ofthese dietary constituents (1). Like humans, Western-type diets can
induce elevated LDL-C and atherosclerosis in certain rodent models(i.e. mice, hamsters, guinea pigs). Therefore, the use of such diets forpromoting atherosclerosis in these models has been a valuable tool
for both gaining more understanding of this disease and testing
therapies that can potentially reverse it.

RepeatDiet 4

Diet 4 = D12109 (40 kcal% Fat,
1.25% Cholesterol, 0.5% Cholic Acid)

FIGURE 1. Oil red O–stained atherosclerotic lesions in aortas of LDLR2/2 mice fed
diets varying in fat, cholesterol, and cholate content. Mice were killed after being fed
defined diets for 12 weeks. Aortas were prepared and stained with oil red O as
described in Methods. One representative aorta from a total of 6 in each of the 4
dietary groups is shown. Graphic representation - for details see reference (38).

is found in high density lipoproteins (HDL-C), which contributes
to their reduced susceptibility to atherosclerosis. Western-type diets
containing moderately high levels of SF (~35 kcal% fat, ), as (cocoa
butter, palm oil, or dairy butter), cholesterol (~0.5 to 1% w/w) andcholic acid (~0.1% to 0.5% w/w), are capable of inducing elevationsin TC and LDL-C and mild atherosclerosis (i.e. cholesterol laden
foam cells, fatty deposits or streaks) in some mouse strains after 12
weeks (14-16). The presence of cholic acid aids cholesterol and fat
absorption, and also suppresses conversion of cholesterol to bile acids(17). This latter effect reduces removal of cholesterol and increases
cholesterol levels (in particular, non-HDL-C) which allows atherosclerosis induction to occur in susceptible mouse strains. While itis possible to induce atherosclerosis in some mice, it is important torealize that the presence of cholic acid can influence transcription
factors controlling genes involved with regulating lipoprotein
metabolism and inflammation, both of which are important in
the development of atherosclerosis (16, 17), and can also promote
gallstones in certain mouse strains (18, 19).
Like mice, commonly used outbred rat strains (i.e. Sprague-Dawley,
Wistar) typically have high levels of HDL-C and low levels of
LDL-C. Western-type diets (~45 kcal% fat as hydrogenatedcoconut oil) or even low-fat diets (~12 kcal% fat as corn oil) withhigh levels of cholesterol (~1% w/w) and cholic acid (0.25% - 0.5%w/w) are capable of promoting elevations in TC and LDL-C in
Sprague-Dawley or Wistar rats (20-22) likely by reducing bile acidproduction (23). Despite such elevations, this alone will not
promote atherosclerosis in rats unless a thyroid hormone inhibitor(2-thiouracil, ~0.5% w/w) is added to the diet (24). However, ratsthat have been selectively bred with spontaneous gene mutations
such as the JCR:LA Corpulent rat can develop hypercholesterolemia
and are sensitive to dietary cholesterol without the need for cholicacid or thyroid hormone inhibitors (25).

Atherosclerosis
Hamsters
Like mice and rats, hamsters typically have a high percentage of
HDL-C. However, Western-type diets high in cholesterol (~0.5%w/w) and SF (15 – 20% butter fat w/w) can elevate plasma TC andLDL-C and promote appreciable atherosclerosis (i.e. fatty streaks,
foam cells) without the use of cholic acid in as little as 6 weeks (26).
Hamsters don’t require cholic acid because dietary cholesterol (evenas high as 1% w/w) has little influence on their bile acid synthesis
pathways (20), allowing excess dietary cholesterol to enter the blood
circulation rather than being converted to bile acids and excreted in
the feces. Furthermore, these animals possess cholesteryl ester transfer
protein (CETP) like humans (but not mice and rats), which allows
the transfer of cholesterol from HDL to LDL particles in plasma.
Certain SFs (relative to unsaturated fats) and cholesterol both havesome ability to promote this pathway (27), and this, in combination
with their ability to reduce LDL-C uptake by the liver (28) allows
for significant elevations in LDL-C and eventual atherosclerosis
induction. These animals are highly sensitive to particular saturated
fatty acids as a Western-type diet high in potent cholesterol-raising
SF from hydrogenated coconut oil (lauric and myristic acids) cancause even more aortic cholesterol accumulation than a highcholesterol (0.15%) diet with a more cholesterol neutral fat suchas cocoa butter (palmitic, oleic and stearic acids) (29).
Additionally, dietary protein type can also influence LDL-C levels
and atherosclerosis as hamsters fed casein and lactalbumin had
higher levels than those fed an equal amount of soy protein, andlike humans, males may be more susceptible than females (11).

Guinea Pigs
Unlike other rodents, guinea pigs have a cholesterol profile similar to
most humans (higher proportion TC as LDL-C) when maintainedon a low fat/low cholesterol diet. Like hamsters, they possess CETP
(30) and do not require cholic acid for atherosclerosis induction andcholesterol elevation (31, 32). They are highly sensitive to changes in
dietary fatty acid composition as Western-type diets high in SF (i.e.
palm kernel oil, ~80% SF) without dietary cholesterol can elevate
TC and LDL-C levels relative to those containing less SF (i.e. palmoil, beef tallow, ~50% SF) (31). The type of protein (i.e. high casein
to soy protein ratio) (32), or carbohydrate (i.e. high sucrose) (33) can
exacerbate the condition. The use of a Western-type diet with addedcholesterol (at least up to 0.3%, w/w) can cause further elevations in
TC and LDL-C and induce atherosclerotic lesions (i.e. fatty streaks)
after 12 weeks (34-36). The carbohydrate to fat ratio also has beenfound to have some importance in promoting atherosclerosis as highcholesterol diets (0.25%, w/w) that are high in carbohydrate (42kcal%) and moderately high in fat (35 kcal%) are more capable ofpromoting atherosclerosis than those low in carbohydrate (11 kcal%)and high in fat (55 kcal%) (37).

Genetically Modified Mouse Models
More recently, mouse models have been developed with genetic
mutations causing them to be more atherosclerosis prone, promoting
atherosclerotic plaques similar to those found in humans. Some wellknown examples of genetically modified mice used in atherosclerosis
research include the LDL receptor (LDLr) null and apolipoprotein E(apoE) null mouse which have mutations that hinder removal of

Where NutriPhenomics® Begins

circulating cholesterol by the liver. The use of Western-type dietswith added cholesterol (0.15% - 1.25% w/w) which are cholic acidfree can induce significant atherosclerotic lesions after 12 weeks in
LDLr null mice (38-40) (FIG. 1, 38). Lesion development is very
dramatic in apoE null mice fed a Western-type diet and beginningstages of atherosclerosis (i.e. fatty streak lesions) can be found at 6
weeks (41). With these mouse models, the main influence on
atherosclerosis has been found to be dietary cholesterol rather
than the level of fat (42-44), but certain threshold levels of dietarycholesterol may exist at least within the context of a low-fat
purified diet (45). While very high fat diets (i.e. 60 kcal% fat) arecapable of inducing some atherosclerosis, the addition of cholesterol
to such diets promotes more atherosclerosis in LDLr null mice (46).
Furthermore, the fatty acid profile and even the carbohydrate
form (i.e. fructose, sucrose) can be manipulated to modify theatherosclerosis phenotype to the researcher’s advantage (39, 42, 47).

References
1. Pearson,TA, Blair,SN, Daniels,SR, Eckel,RH, Fair,JM, Fortmann,SP, Franklin,BA,
Goldstein,LB, Greenland,P, Grundy,SM, Hong,Y, Miller,NH, Lauer,RM, Ockene,IS,
Sacco,RL, Sallis,JF, Jr., Smith,SC, Jr., Stone,NJ, Taubert,KA: AHA Guidelines for Primary
Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide
to Comprehensive Risk Reduction for Adult Patients Without Coronary or Other
Atherosclerotic Vascular Diseases. American Heart Association Science Advisory and
Coordinating Committee. Circulation 106:388-391, 2002
2. Libby,P, Ridker,PM, Maseri,A: Inflammation and Atherosclerosis.
Circulation 105:1135-1143, 2002
3. Van Gaal,LF, Mertens,IL, De Block,CE: Mechanisms linking obesity withcardiovascular disease. Nature 444:875-880, 2006
4. Hegsted,DM, McGandy,RB, Myers,ML, Stare,FJ: Quantitative effects of dietary fat onserum cholesterol in man. Am J Clin Nutr 17:281-295, 1965
5. Cybulsky,MI, Lichtman,AH, Haijra,L, Iiyama,K. Leukocyte adhesion molecules inatherogenesis: Clinica Chimica Acta 286:207-218, 1999
6. Thigpen,JE, Setchell,KD, Ahlmark,KB, Locklear,J, Spahr,T, Caviness,GF, Goelz,MF,
Haseman,JK, Newbold,RR, Forsythe,DB: Phytoestrogen content of purified, open- andclosed-formula laboratory animal diets. Lab Anim Sci. 49:530-536, 1999
7. Brown,NM, Setchell,KD: Animal models impacted by phytoestrogens in commercial
chow: implications for pathways influenced by hormones. Lab Invest 81:735-747, 2001
8. Mezei,O, Banz,WJ, Steger,RW, Peluso,MR, Winters,TA, Shay,N: Soy isoflavones exert
antidiabetic and hypolipidemic effects through the PPAR pathways in obese Zucker rats
and murine RAW 264.7 cells. J Nutr. 133:1238-1243, 2003
9. Kirk E, Sutherland P, Wang S, Chait A, LeBoeuf R: Dietary isoflavones reduce plasmacholesterol and atherosclerosis in C57BL/6 mice but not LDL receptor-deficient mice.
J Nutr 128:954-959, 1998
10. Torvar-Palacio C, Potter SM, Hafermann JC, Shay NF: Intake of soy protein and soy
protein extracts influences lipid metabolism and hepatic gene expression in gerbils.
J Nutr 128:839-42, 1998
11. Blair,RM, Appt,SE, Bennetau-Pelissero,C, Clarkson,TB, Anthony,MS, Lamothe,V,
Potter,SM: Dietary soy and soy isoflavones have gender-specific effects on plasma lipids inGolden Syrian F1B Hybrid Hamsters. J Nutr 1323585-3591, 2002
12. Ascencio,C, Torres,N, Isoard-Acosta, F, Gomez-Perez,FJ, Hernandez-Pando,R, Tovar,AR:
Soy protein affects serum insulin and hepatic SREBP-1 mRNA and reduces fatty liverin rats. J Nutr 134:522-529, 2004
13. Adams,MR, Golden,DL, Anthony,MS, Register,RC, and Koudy Williams,J: The
inhibibory effect of soy protein isolate on atherosclerosis in mice does not require thepresence of LDL receptors or alteration of plasma lipoproteins. J Nutr 132:43-49, 2002
14. Nishina,PM, Wang,J, Toyofuku,W, Kuypers,FA, Ishida,BY: Atherosclerosis and plasma
and liver lipids in nine inbred strains of mice. Lipids 28:599-605, 1993
15. Nishina,PM, Lowe,S, Verstuyft,J, Naggert,JK, Kuypers,FA, Paigen,B: Effects of dietaryfats from animal and plant sources on diet-induced fatty streak lesions in C57BL/6J mice.
J Lipid Res. 34:1413-1422, 1993
16. Nishina,PM, Verstuyft,J, Paigen,B: Synthetic low and high fat diets for the study ofatherosclerosis in the mouse. J Lipid Res 31:859-869, 1990
17. Ando,H, Tsuruoka,S, Yamamoto,H, Takamura,T, Kaneko,S, Fujimura,A: Regulation ofcholesterol 7alpha-hydroxylase mRNA expression in C57BL/6 mice fed an
atherogenic diet. Atherosclerosis 178(2):265-269, 2005
18. Xu,G, Zhao,L, Fuchs,M: Differences between hepatic and biliary lipid metabolism andsecretion in genetically gallstone-susceptible and gallstone-resistant mice.
Chin Med J (Engl.) 115:1292-1295, 2002
19. Khanuja,B, Cheah,YC, Hunt,M, Nishina,PM, Wang,DQ, Chen,HW, Billheimer,JT,
Carey,MC, Paigen,B: Lith1, a major gene affecting cholesterol gallstone formation among
inbred strains of mice. Proc Natl Acad Sci USA 92(17):7729-7733, 1995

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Atherosclerosis
References

Contact our Resource Center for valuable insight from morethan 25 years of product experience in the field of atherosclerosis.
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BioDAQ Episodic Intake Monitor
BioDAQ E2 Episodic monitoring system measures thead libitum food and water intake behavior of singly
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20. Jeong,WI, Jeong,DH, Do,SH, Kim,YK, Park,HY, Kwon,OD, Kim,TH, Jeong,KS: Mild
hepatic fibrosis in cholesterol and sodium cholate diet-fed rats.
J Vet Med Sci 67:235-242, 2005
21. Yokozawa,T, Cho,EJ, Sasaki,S, Satoh,A, Okamoto,T, Sei,Y: The protective role of Chineseprescription kangen-karyu extract on diet-induced hypercholesterolemia in rats.
Biol Pharm Bull 29(4):760-765, 2006
22. Zulet,MA, Barber,A, Garcin,H, Higueret,P, Martinez,JA: Alterations in carbohydrate andlipid metabolism induced by a diet rich in coconut oil and cholesterol in a rat model.
J Am Coll Nutr 18(1):36-42, 1999
23. Horton,JD, Cuthbert,JA, Spady,DK: Regulation of hepatic 7 alpha-hydroxylase expression
and response to dietary cholesterol in the rat and hamster.
J Biol Chem 270:5381-5387, 1995
24. Joris,I, Zand,T, Nunnari,JJ, Krolikowski,FJ, Majno,G: Studies on the pathogenesis ofatherosclerosis. I. Adhesion and emigration of mononuclear cells in the aorta ofhypercholesterolemic rats. Am J Pathol 113(3):341-358, 1983
25. Russell,JC, Graham,SE, Richardson,M: Cardiovascular disease in the JCR:LA-cp rat.
Mol Cell Biochem 188(1-2):113-126, 1998
26. Kahlon,TS, Chow,FI, Irving,DW, Sayre,RN: Cholesterol response and foam cell
formation in hamsters fed two levels of saturated fat and various levels of cholesterol.
Nutr Res 16(8):1353-1368, 1996
27. Kurushima, H, Hayashi,K, Shingu,T, Kuga,Y, Ohtani,H, Okura,Y, Tanaka,K, Yasunobu,Y,
Nomura,K, Kajiyama,G: Opposite effects on cholesterol metabolism and theirmechanisms induced by dietary oleic acid and palmitic acid in hamsters.
Biochim Biophys Acta 1258(3):251-256, 1995
28. Dietschy,JM: Dietary fatty acids and the regulation of plasma low density lipoproteincholesterol concentrations. J Nutr 128:444S-448S, 1998
29. Alexaki,A, Wilson,TA, Atallah,MT, Handelman,G, Nicolosi,RJ: Hamsters fed diets highin saturated fat have increased cholesterol accumulation and cytokine production in theaortic arch compared with cholesterol-fed hamsters with moderately elevated plasma
non-HDL cholesterol concentrations. J Nutr 134:410-415, 2004
30. Fernandez,ML, Volek,JS: Guinea pigs: A suitable animal model to study lipoprotein
metabolism, atherosclerosis and inflammation. Nutr Metab 3:17, 2006
http://www.nutritionandmetabolism.com/content/3/1/17
31. Fernandez,ML, Lin,EC, McNamara,DJ: Differential effects of saturated fatty acids on
low density lipoprotein metabolism in the guinea pig. J Lipid Res 33: 1833-1842, 1992
32. Fernandez,ML, Wilson,TA, Conde,K, Vergara-Jimenez,M, Nicolosi,RJ: Hamsters andguinea pigs differ in their plasma lipoprotein cholesterol distribution when fed diets varying
in animal protein, soluble fiber, or cholesterol content. J Nutr 129:1323-1332, 1999
33. Fernandez,ML, Vergara-Jimenez,M, Conde,K, Abdel-Fattah,G: Dietary carbohydrate
type and fat amount alter VLDL and LDL metabolism in guinea pigs.
J Nutr 126:2494-2504, 1996
34. Lin,EC, Fernandez,ML, Tosca,MA, McNamara,DJ: Regulation of hepatic LDL
metabolism in the guinea pig by dietary fat and cholesterol. J Lipid Res 35:446-457, 1994
35. Cos,E, Ramjiganesh,T, Roy,S, Yoganathan,S, Nicolosi,RJ, Fernandez,ML: Soluble fiberand soybean protein reduce atherosclerotic lesions in guinea pigs. Sex and hormonal
status determine lesion extension. Lipids 36:1209-1216, 2001
36. Zern,TL, West,KL, Fernandez,ML: Grape polyphenols decrease plasma triglycerides
and cholesterol accumulation in the aorta of ovariectomized guinea pigs.
J Nutr 133:2268-2272, 2003
37. Torres-Gonzalez,M, Volek,JS, Sharman,M, Contois,JH, Fernandez,ML: Dietarycarbohydrate and cholesterol influence the number of particles and distributions oflipoprotein subfractions in guinea pigs. J Nutr Biochem, 17(11):773-9, 2006
38. Lichtman,AH, Clinton,SK, Iiyama,K, Connelly,PW, Libby,P, Cybulsky,MI:
Hyperlipidemia and atherosclerotic lesion development in LDL receptor-deficient
mice fed defined semipurified diets with and without cholate.
Arterioscler Thromb Vasc Biol 19:1938-1944, 1999
39. Collins,AR, Meehan,WP, Kintscher,U, Jackson,S, Wakino,S, Noh,G, Palinski,W,
Hsueh,WA, Law,RE: Troglitazone inhibits formation of early atherosclerotic lesions indiabetic and nondiabetic low density lipoprotein receptor-deficient mice.
Arterioscler Thromb Vasc Biol 21:365-371, 2001
40. Joseph,SB, McKilligin,E, Pei,L, Watson,MA, Collins,AR, Laffitte,BA, Chen,M, Noh,G,Goodman,J, Hagger,GN, Tran,J, Tippin,TK, Wang,X, Lusis,AJ, Hsueh,WA, Law,RE,
Collins,JL, Willson,TM, Tontonoz,P: Synthetic LXR ligand inhibits the development of
atherosclerosis in mice. Proc Natl Acad Sci U.S.A. 99:7604-7609, 2002
41. Nakashima,Y, Plump,AS, Raines,EW, Breslow,JL, Ross,R: ApoE-deficient mice develop
lesions of all phases of atherosclerosis throughout the arterial tree.
Arteroscler Thromb 14:133-140, 1994
42. Merat,S, Casanada,F, Sutphin,M, Palinski,W, Reaven,PD: Western-type diets induce
insulin resistance and hyperinsulinemia in LDL receptor-deficient mice but do notincrease aortic atherosclerosis compared with normoinsulinemic mice in which similar
plasma cholesterol levels are achieved by a fructose-rich diet.
Arterioscler Thromb Vasc Biol 19:1223-1230, 1999
43. Wu,L, Vikramadithyan,R, Yu,S, Pau,Cl, Hu,Y, Goldberg,I, Dansky,HM: Addition of
dietary fat to cholesterol in the diets of LDL receptor knockout mice: effects on plasma
insulin, lipoproteins, and atherosclerosis. J Lipid Res 47:2215-2222, 2006.
44. Davis,HR, Compton,DS, Hoos,L, Tetzloff: Ezetimibe, an important cholesterol
absorption inhibitor, inhibits the development of atherosclerosis in apoE knockout mice.
Arterioscler Thromb Vasc Biol 21: 2032-2038, 2001
45. Teupser,D, Persky,AD, Breslow,JL: Induction of atherosclerosis by low-fat, semisynthetic
diets in LDL receptor-deficient C57BL/6J and FVB/NJ mice: comparison of lesions of
the aortic root, brachiocephalic artery, and whole aorta (en face measurement).
Arterioscler Thromb Vasc Biol 23:1907-1913, 2003
46. Subramanian,S, Han,CY, Chiba,T, McMillen,TS, Wang,SA, Haw,A, Kirk,EA,
O’Brien,KD, Chait,A: Dietary cholesterol worsens adipose tissue macrophage
accumulation and atherosclerosis in obese LDL receptor-deficient mice.
Arterioscler Thromb Vasc Biol 28(4): 685-691, 2008
47. Merkel,M, Velez-Carrasco,W, Hudgins,LC, Breslow,JL: Compared with saturated fatty
acids, dietary monounsaturated fatty acids and carbohydrates increase atherosclerosis and
VLDL cholesterol levels in LDL receptor-deficient, but not apolipoprotein E-deficient,mice. Proc Natl Acad Sci U.S.A. 98:13294-13299, 2001