Table 3.
Impact of dietary cholesterol in mouse models of atherosclerosis.
| Study/Mouse Model | Diet | Age | Stage of Disease |
|---|---|---|---|
| C57BL/6J | |||
| Lee et al., 2017 [51] | 30% fat, 5% cholesterol and 2% cholic acid | Increased serum cholesterol levels Atheroma lesions and extreme hepatic damage |
|
| Paigen et al., 1987 [52] C57BL/6 mouse |
1.25% cholesterol, 15% fat, and 0.5% cholic acid (toxic atherogenic diet) | Diet for 14 weeks | Atheroma lesions Discrete hypercholesterolemia |
| Vergnes et al., 2003 [26]. C57BL mice |
Different diets (1.25% cholesterol, 0.5% sodium cholate, and 7.5% cocoa butter, and three other diets which omitted one of the three components of the atherogenic diet) | Males at 3 months of age were fed with the diet for 3 weeks | Dietary cholesterol induces the expression of inflammatory genes Cholate induces the expression of extracellular matrix deposition genes such as collagen |
| Studies in LDLr-deficient mice | |||
| Ishibashi et al., 1994 [53]. |
1.25% cholesterol, 7.5% cocoa butter, 7.5% casein, and 0.5% cholic acid | Diet for 6, 7, or 8 months | Severe hypercholesterolemia Atheroma lesions in the vascular wall |
| Lichtman et al., 1999 [54] | 0.5% and 1.25% of cholesterol to a high-fat diet | Males at 8 to 12 weeks of age were fed with the diet for 12 weeks | Lesion plaque formation in a dose-dependent manner |
| Hartvigsen et al., 2007 [55] | Western-type diet, 0.06% cholesterol/21% milk fat, or a cholesterol-enriched diet, 1% cholesterol/4.4% fat | Males were fed with the diet for 28 weeks | Atherosclerotic lesions |
| Subramanian et al., 2008 [56] | Carbohydrate-rich diet with 0.15% cholesterol | Males at 8 weeks old were fed with diet for 24 weeks | Accumulation of macrophages in adipose tissue Acceleration of atherosclerosis |
| Teupser et al. 2003 [57] LDLr-/- mice in C57BL/6J |
4.3% fat in combination with 0.02% 0.15%, 0.30%, or 0.50% cholesterol | Mice at 28 days of age were fed the diet for 16 weeks (20 weeks of age) | Atherosclerosis in aortic root, brachiocephalic artery and whole aorta |
| Wu et al., 2006 [58] | 0.15% cholesterol versus 0.03% cholesterol with high fat in each diet | Diet 20 or 40 weeks | Lesion size was bigger in mice fed 0.15% cholesterol versus 0.03% cholesterol Addition of fat to a cholesterol-rich diet did not increase atherosclerotic lesion hypertriglyceridemia |
| Ma et al., 2012 [59] | 21% fat, 0.15% cholesterol | Males at 8 weeks were fed with the diet for 1, 3, 6, 9, 12 months | Before 3 months: slight atherosclerotic lesions in aortic roots and innominate artery At 3 months: advanced lesions in the aortic sinus At 6–9 months: advanced lesions in the innominate artery |
| Joyce et al., 2006 [60] | 0.02% cholesterol and 4% fat or 0.2% cholesterol and 21.2% fat | Diet 4, 9, or 12 weeks prior to sacrifice | Increased hepatic content of cholesterol and aggravated aortic root atherosclerosis in LDLr-/- mice that overexpressed ABCA1 in the liver |
| Kennedy et al., 2009 [61] LDLr-/-CD36-/- mice |
High-cholesterol diet | Diet for 12 weeks | Atherosclerotic lesions |
| Fuller et al., 2014 [62]. LDLr-/- SRBI-/- |
High-cholesterol high-fat high-cholesterol high-fat high-cholesterol cholate diet |
Females at 10–12 weeks of age were fed 12 weeks with the atherogenic diet | Occluded coronary arteries Accumulation of platelets in atherosclerotic plaque in coronary arteries (thrombosis) Myocardial fibrosis Increased circulating Ly6Chi monocytes |
| Studies in apoE-deficient mice | |||
| Zhang et al., 1994 [63] Partially deficient in apoE |
15.8% fat, 1.25% cholesterol, and 0.5% cholate | Beginning at 8 weeks of age, mice were fed 6 or 12 weeks with the diet | Atheroma lesions |
| Nakashima et al., 1994 [64] |
Western-type diet, containing 21% fat, 0.15% cholesterol and 19.5% casein without sodium cholate | Males at 5 weeks of age were fed the diet until 6, 8, 10, 15, 20, 30, and 40 weeks of age | Advanced plaques Development of fibrous cap, presence of smooth muscle cell and adhesion of monocytes |
| Joyce et al., 2002 [65] ABCA1-Tg apoE-/- |
1.25% cholesterol and 0.5% cholic acid | Mice at 2–3 months of age were maintained on the diet for 15 weeks before sacrifice | Overexpression of ABCA1 increased apoB-lipoprotein and HDL levels in plasma and reduced atherosclerosis in vivo |
| Johnson et al., 2001 [66] | 0.15% cholesterol into a high-fat diet | Seven-week-old mice were fed the diet for 14 months | Plaque rupture in the brachiocephalic artery Lesions with intraplaque hemorrhage |
| Bond et al., 2011 [67]. |
Cholesterol diet | Lesions in the brachiocephalic artery |
|
| Acin et al., 2005 [68] | Different fat-enriched diet and cholesterol with or no unsaturated sources such as extra virgin olive oil (EVOO) | 2-month-old mice were fed with different diets for 10 weeks | Reduced lesion formation with EVOO Cholesterol prevented the beneficial effects of unsaturated fat from EVOO |
| Swirski et al., 2007 [69] | Cholesterol diet | Beginning at 10 weeks of age, mice were fed 20–25 weeks with the diet | Accelerated atherosclerosis by increasing Ly6Chi |
| Mailer et al., 2017 [70] | Cholesterol diet | Mice at 8–10 weeks of age were fed for 4, 12, or 24 weeks with the diet | Accelerated atherosclerosis by activating T cell receptor signaling |
| Ito et al., 2016 (in combination with LXRβ-/-) [71] | Cholesterol diet | Diet for 8, 12, or 16 weeks | Accelerated atherosclerosis and production of autoantibodies and B cell expansion |
| Studies in “humanized” ApoB-100 and ApoE3*Leiden transgenic mice | |||
| Purcell-Huynh et al., 1998 [72] | 16% fat and 1.25% cholesterol | Males and females at 5 weeks of age were fed the diet for 5 or 8 weeks | Severe hypercholesterolemia and atherosclerosis |
| Laplante et al. 2013 [73] LDLr-/-TgApoB100 and LDLr-/TgApoB100IGFII |
Standard chow, 0.2% cholesterol diet, high-fat diet or high-fat 0.2% cholesterol diet | Males aged 6 weeks were fed the diet for 6 months | Cholesterol accelerates lesion formation in both LDLr-/-TgApoB100 and LDLr-/-TgApoB100IGFII. |
| Van Vlijmen et al., 1994 [74] ApoE*3Leiden transgenic mice |
High cholesterol | At 8–10 weeks old age, mice were fed for 6 weeks with the diet | Hypercholesterolemia and atherosclerotic lesions in the whole aorta and carotid arteries |
| Kleemann et al., 2007 [75] ApoE*3Leiden transgenic mice |
0%, 0.25%, and 1.25% cholesterol | Female E3L mice at 12 weeks old were treated with diet for 10 weeks | Hypercholesterolemia and atherosclerosis |