Asia Pacific J Clin Nutr (1997) 6(1): 17-21

Vervet monkeys and whole-food diets for studying the effects of dietary lipids on plasma lipoprotein metabolism and atherosclerosis

AJS Benadé DSc, JE Fincham, CM Smuts MSc, MJ Weight, PJ van Jaarsveld PhD, M Kruger

National Research Programme for Nutritional Intervention Medical Research Council, Tygerberg, South Africa

---

It is well established that some species of nonhuman primates are models of choice for polygenic hyperlipoproteinaemia and atherosclerosis induced and promoted by diets as occur in man. The Vervet monkey (Cercopithecus aethiops) has proved to be one such model. Our group has used this model extensively to determine the effects of a variety of dietary lipid components on plasma lipoprotein metabolism and atherosclerosis against a background of a Western atherogenic or prudent diet. The diets fed in all these studies were formulated entirely from cooked foods that are normal components of Westernised diet with no extra synthetic cholesterol added.

This model has been used successfully to evaluate the effect of fish oil, amount and degree of dietary fat unsaturation and w-6/w-3 fatty acid ratio and lipid-lowering agents on plasma lipoprotein metabolism and atherosclerosis. Dietary manipulation in this model is simple, relatively inexpensive and offers almost unlimited options for future dietary intervention studies.

Key words: African Green monkey, dietary lipids, plasma lipoprotein metabolism, atherosclerosis

---

Introduction

It is well established that some species of non-human primates are models of choice for polygenic hyperlipoproteinaemia and atherosclerosis induced and promoted by diets as occur in man^1-9. The Vervet or African Green monkey (Cercopithecus aethiops) has proved to be an excellent model for studying the effects of a variety of dietary lipid components on plasma lipoprotein metabolism^3,4,9-12 and atherosclerosis^13-16. The potential for using this primate to study the effect of lipid-lowering agents on plasma lipoprotein metabolism and atherosclerosis was recently demonstrated¹⁷.

Direct comparison of results from the various studies is difficult because of differences between species and diets administered to experimental animals of the same species. The purpose of this communication is therefore to review results of our own studies which used the African Green monkey, and diets that are realistic for man^{1,11-13,15-17}.

Materials and methods

Vervet monkeys were all healthy and conditioned to the laboratory environment for six months or more^18,19. Diets fed were either an average Western diet (WD), a prudent diet (PD) or a high carbohydrate diet (HCD), which have been described in detail elsewhere^1,20. The period of time diets were fed ranged from four to 47 months. Diets were composed entirely of normal food items for humans without any added cholesterol and spanned a realistic nutritional range.

Comparison of the effect of the amount and degree of unsaturation of dietary fat on plasma low density lipoproteins

Kruger et al¹² studied the effects of the degree of unsaturation and of the amount of dietary fat on low density lipoprotein (LDL) concentration and composition in the African Green (Vervet) monkeys (12 females; age 1.5-4.5 years). Animals received diets with fat contents of 41, 31 and 18% energy each with a low and high polyunsaturated to saturated fatty acid ratio (P/S; 0.27-0.38 and 1.13-1.47; major fatty acids were palmitic and linoleic acids) for a period of two months. Cholesterol content of the diet was low (6.0-9.3mg/100Kcal). LDL cholesterol concentrations showed significant decreases when the dietary fat content decreased from 31 to 18% of energy. Dietary P/S ratio only affected LDL cholesterol concentrations during moderate (31% of energy) fat intake. Low density lipoprotein cholesterol increased with a decrease in dietary P/S. The changes in LDL cholesterol concentrations were the result of changes in the number of circulating LDL particles as the molecular composition was not significantly affected between dietary periods. Dietary fat changes had no influence on the high density lipoprotein cholesterol and plasma triacylglycerol concentrations. During the high P/S diets, the percentage of linoleic acid (18:2 w6) in LDL esterified cholesterol (CE) and adipose tissue triacylglycerol (TAG) increased as compared to the low P/S diets.

Results of this study provides evidence that the amount of dietary fat had a greater influence on plasma cholesterol concentration than a moderate change in dietary P/S in Vervets. The effects of dietary fat on plasma cholesterol were mainly through changes in LDL cholesterol concentrations. The animals showed marked individual differences in LDL cholesterol concentration response to both the amount and the degree of unsaturation of fat in the diet.

The finding that LDL particle mass was also not influenced significantly by dietary fat changes supports findings in both Vervets¹³ and humans²¹. The loading of LDL with esterified and unesterified cholesterol and increased LDL particle mass reported in some studies in non-human primates fed an atherogenic diet probably resulted from excessive cholesterol intake^22-24,28.

The influence of fish oil supplementation on plasma lipoproteins and arterial lipids in Vervets¹⁶

Details of the study were described previously¹⁶. Briefly, the experimental design was as follows: Vervets (20 males, 17 females; all adults) were divided into four comparable groups, two groups were retained on the Western atherogenic diet (WAD), based on milk, eggs, meat, legumes, cereals, sugar, fruit, vegetables, butter and sunflower oil (35% E fat, 31.0 mg chol/100Kcal), one of which was supplemented with fish oil (WAD/FO; n = 9), while the other received a sunflower oil (WAD/SO; n = 9) supplement. The remaining two groups were changed from the WAD to a high carbohydrate diet (HCD). One group was supplemented with the same FO supplement (HCD/FO; n = 9) and the other group received the sunflower oil (HCD/SO; n = 10) supplement. Nine female Vervets that were never exposed to the WAD served as a reference group and received a high carbohydrate diet. Vervets were terminated after 20 months.

Fish oil supplementation did not change the cholesterol concentrations of plasma cholesterol or LDL significantly (Table 1). Vervets of the WAD/FO group had an increased (2.7 times; p£0.001) content of total cholesterol in their aortic intima compared to the WAD/SO group. The same trend was also evident after FO was supplemented to the HCD.

Table 1. The effect of fish oil on lipoprotein and arterial total cholesterol levels¹⁶

	WAD/SO n=9	WAD/FO n=9	HCD/SO n=10	HCD/FO n=9	HCD n=9
Plasma (mg/dL)	333 (125.2)	345 (121.0)	146 (23.1)	144 (20.6)	181 (24.2)
LDL (mg/dL)	300.9 (158.9)	265.9 (134.2)	49.5 (21.2)	49.7 (13.6)	86.9 (26.6)
Intima (mg/mg protein)	32.5 (26.6)	89.2† (78.3)	44.2 (70.9)	83.7* (125.2)	10.5 (4.9)

WAD: Western atherogenic diet; SO: Sunflower oil; FO: Fish oil; HCD: High carbohydrate diet; (values in parenthesis are ± SD)
Significant difference between WAD/FO and WAD/SO or HCD/FO and HCD/SO: ^*p<0.01; ^†p<0.001

---

EPA was increased 7.5 and 6.5-fold respectively (both p£ 0.001) in plasma and aortic intima PC (Table 2). Dihomogamma-linolenic acid (C20:3 w6; DGLA p£ 0.01) and arachidonic acid (C20:4 w6; AA p£0.001) levels were reduced in the plasma PC after FO supplementation of the WAD, and similar effects were seen after supplementing the HCD with FO. In the aorta intima the AA was also reduced (P£ 0.001) on the WAD/FO. Docosahexaenoic acid (C22:6 w3; DHA) was also increased after FO supplementation. In the plasma and aorta intima PC, EPA and AA respectively demonstrated the strongest negative and positive correlations with the intimal CE and FC contents (Table 3).

Table 2. The effect of fish oil on the fatty acid composition of plasma and intima phosphatidylcholine fatty acids¹⁶

	WAD/SO n=9	WAD/FO n=9	HCD/SO n=10	HCD/FO n=9	HCD n=9
Plasma
C18:2w6	25.6 (2.2)	18.1† (2.1)	33.3 (2.9)	23.6a* (1.6)	31.5 (1.5)
C20:3w6	1.5 (0.1)	1.2* (0.1)	2.6 (1.4)	1.1a* (0.3)	3.9 (1.2)
C20:4w6	12.1 (1.0)	9.4† (0.5)	8.0 (1.0)	5.9† (0.7)	8.8 (0.8)
C20:5w3	0.8 (0.1)	6.0† (0.7)	0.4 (0.1)	5.3a* (1.1)	0.3 (0.1)
C22:6w3	5.5 (1.0)	8.2† (1.5)	3.0 (0.4)	7.6† (0.8)	3.0 (0.5)
Intima
C18:2w6	5.7 (0.8)	7.4* (1.3)	6.3 (1.0)	7.0 (1.7)	5.1 (0.8)
C20:3w6	1.0 (0.3)	1.3 (0.2)	1.1 (0.4)	1.1 (0.3)	1.0 (0.2)
C20:4w6	19.6 (1.9)	15.0† (1.8)	18.0 (2.8)	15.5 (2.5)	20.4 (1.9)
C20:5w3	0.2 (0.1)	1.3† (0.4)	0.1 (0.1)	0.6a* (0.1)	ND
C22:6w3	3.1 (0.7)	3.7 (0.9)	2.1 (0.5)	3.0* (0.7)	2.3 (0.5)

WAD Western atherogenic diet; HCD High carbohydrate diet
SO Sunflower oil; FO Fish oil; ^aMales; ND Not detected
Significant difference between WAD/FO and WAD/SO or HCD/FO and HCD/SO. ^*p<0.01; ^†p<0.001

Table 3. Correlation coefficients (r) and p-values between the esterified cholesterol (CE) and free cholesterol (FC) content of the aorta intima and plasma and intimal phosphatidylcholine (PC) fatty acids¹⁶.

	Intima-FC		Intima-CE
PC Fatty acid	r	p	R	p
Plasma
C20:4w6	-0.66	0.0029	-0.53	0.0245
C20:5w3	0.75	0.0004	0.57	0.0126
Intima
C20:4w6	-0.73	0.0007	-0.72	0.0005
C20:5w3	0.78	0.0001	0.59	0.0095

The effect of diet on the metabolism of EPA²⁷

Controversy surrounds the beneficial effects of EPA on lipo-protein metabolism because researchers showed that EPA does lower plasma cholesterol concentrations in primates²⁵ while others suggested a cholesterol elevating effect¹⁵. Although many factors could possibly explain these divergent results obtained with EPA, difference in the diets which were supplemented could be important²⁶.

In a study reported by van Rooyen²⁷, Vervet monkeys (20 adult females) receiving either a WAD or HCD were supplemented with (2400 mg/day) EPA concentrate (Callandish Pharmaceuticals, 50% free acid) for 24 weeks after which time EPA supplementation was withdrawn. Animals then continued on their respective diets for a further 12 weeks during which time the EPA contents of the erythrocyte membrane phosphatidylcholine (EMB-PC), phosphatidylethanolamine (EMB-PE), plasma CE and TAG were carefully monitored. This information was then used to calculate the relative rates of disappearance from the various tissues.

Although the rates of disappearance differed significantly between the various tissue compartments, rates of disappearance of EPA in the WAD animals were invariably statistically significantly slower than in the HCD animals (Table 4). These results are in agreement with the results from LDL turnover studies by Weight et al¹¹ who reported a slower rate of clearance of ¹²⁵iodine labelled LDL in monkeys fed a WAD compared to animals fed a prudent HCD diet, suggesting a slower rate of metabolism of plasma lipoprotein in animals fed a WAD. In the EPA treated groups, plasma total cholesterol levels increased by 17% in association with the WAD and decreased by 20.8% in association with the HCD. High density lipoprotein cholesterol levels were reduced in both diets by EPA supplementation.

Table 4. Summary of the comparison of the estimated half-life (t½) (median of the individual median measurement in days) of eicosapentaenoic acid (EPA)²⁷.

Compartment	WAD	HCD
EMB-PE	43.5	31.3
EMB-PC	34.3	22.6
Plasma CE	23.5	14.1
Plasma TAG	17.4	9.4

EMB: Erythrocyte membrane; PC: Phosphatidylcholine; PE: Phospha-tidylethanolamine; CE: Esterified cholesterol; TAG: Triacylglycerol; WAD: Western atherogenic diet; HCD: High carbohydrate diet

---

The effect of cholesterol and type of fat in the diet on the LDL composition of the African Green monkey²⁸

Malan²⁸ studied the effect of cholesterol and type of fat in the diet on the LDL composition of African Green monkeys (15 adult males) receiving diets containing a constant amount of fat (40% of energy) and which varied only in the amount of cholesterol (16.4 or4.0 mg/100kcal) and in the type of fat (P/S; 0.3 or 1.2) present in the diet. Cholesterol was found to exert a significant and independent effect on the LDL total cholesterol, LDL-CE, LDL free cholesterol (LDL-FC), LDL apolipoprotein B (LDL-apoB) and LDL total phospholipid (LDL-TPL) concentrations.

There was significant interaction between cholesterol and P/S in their effect on the LDL composition. The effect of the cholesterol was significant only at low P/S ratio. The high cholesterol, low P/S diet was characterised by an enrichment of the LDL particles with CE at the expense of TAG as well as by a significant increase in the LDL molecular weight (MW).

Although the P/S also exerted significant effects on the LDL composition, it was less marked than that of cholesterol. At low cholesterol diets, the P/S significantly affected the CE and FC content of the LDL and the LDL-MW which were all relatively increased during the high P/S diets compared to the low P/S diets. At a high cholesterol content in the diet, the increase in the P/S caused significant decreases in the TPL content of the LDL and in LDL-MW.

Results of this study concerning the LDL compositional changes in response to increased intake of dietary cholesterol are consistent with those from previous studies using nonhuman primates.

Atherogenic and prudent diet experiments^{1,13,15,20,29}

Five papers were published based on results of an experiment which incorporated major improvements in methodology in relation to atherosclerosis, diets and clinical control. One hundred adult female, non-pregnant, premenopausal Vervets were used. Environment in terms of photoperiod, temperature, air circulation and access by potential disease vectors was controlled.

Fixation of arteries for microscopy is the most critical part of the methodology to optimise visualisation of atherosclerosis^1,17,30. An improved procedure commenced under surgical anaesthesia by flushing of the heart and arterial system with isotonic saline at physiological pressure (100 mm Hg) and flow, which prevented agonal clotting¹. Perfusion of the arteries with fixative via the left ventricle, with lung function supported by a ventilator, followed immediately after the flushing, with the heart still beating. This method enhanced qualitative results and enabled definition of atherosclerosis by precise cellular, extra-cellular and morphometric criteria for the first time, including peripheral and coronary atherosclerosis. As a result, a strong positive relationship between athero-sclerosis, hypercholesterolaemia and known dietary risks, was confirmed in adult female Vervets. The prudent diet was not associated with definitive atherogenesis, but failed to regress components of advanced atherosclerotic plaque, such as cholesterol crystals, calcification and fibrosis, within 20 months. This implied that for Vervets the prudent diet would be more effective for preventing atherosclerosis than treating advanced lesions, and this may well apply to people. Significant coronary atherosclerosis and myocardial sequelae, such as infarction and fibrosis, did not develop in adult females at dietary risk for 47 months.

In addition to measurement of true atherosclerosis, 50 variables were monitored at regular intervals, and included plasma lipograms, 23 chemical pathology variables, haema-tology and body weights²⁰. Treatment durations of 15, 20, 27 and 47 months defined a time scale of atherosclerosis in response to well controlled dietary challenge in adult females. Atherogenic and prudent diets were realistic for Westernised people, and no extra pure cholesterol was added because this is not relevant to the human experience. Dietary compliance was proven by measuring food intake. The other treatments were constant exposure to either atherogenic, prudent or reference (= negative control high carbohydrate) diets. The reference diet was realistic for Third World people. Mean plasma total cholesterols (mg/dL) in Vervets fed the respective diets stabilised at 147 (reference diet), 174 (prudent diet) and 376 (atherogenic diet). Dietary change from atherogenic for 20 months, back to prudent for 27 months was tested, and the result confirmed that the prudent diet completely reversed hyperlipidaemia. The phenomenon of hyper- and hypocholesterolaemic responders was confirmed and this models a similar situation with polygenic atherosclerosis in people. Hypercholesterolaemic response ranged between individuals from 81 to 505 mg/dL, or 623%. Red blood cells, platelets and associated parameters increased in association with the atherogenic diet compared to the prudent diet, haemoglobin was the same and haemoglobin per red cell decreased. Activities of rate limiting enzymes for cholesterol synthesis in liver were not conclusively related to diet. Dietary ascorbic acid requirements under the conditions of the experiment were defined. Statistically significant increases in calcium, zinc, vitamin E, and decreased vitamin B₆ were associated with the atherogenic compared to the prudent diet (in plasma or serum)²⁰. A contribution to definition of folic acid and vitamin B₁₂ requirements resulted from a separate study which detected very low folate status after chronic intakes of the atherogenic diet³¹.

Atlantic pilchard fish oil^15,16

Supplementation of atherogenic and therapeutic diets with fish oil was for 20 months, and commenced after long-term (average of 24.5 months) exposures to the atherogenic diet to accelerate progression of atherosclerosis. Processing of peripheral, coronary and cerebral arteries, and aortas, for detection of atherosclerosis was again improved in that saline and fixative used to perfuse the circulation during anaesthesia were continuously oxygenated. This is reported to prevent terminal sloughing of endothelium due to hypoxia, which creates false lesions³⁰. Cerebral arteries were perfused by canulation of a common carotid artery, with the opposite carotid tied-off to prevent short circuiting of perfusate by shunting through vertebral arteries. Jugular veins were severed to prevent pressure build-up in the cerebral circulation.

Atlantic pilchard (Sardinops oscellata) fish oil is relatively rich in eicosapentaenoic and docosahexaenoic w3 polyunsaturated fatty acids. In control groups, sunflower (Helianthus annuus) replaced the fish oil to supply the same quantity of polyunsaturate (m/m) in the form of 18:2 w6 linoleic acid. Twenty adult male and 17 adult female Vervets were used in this study, which enabled confirmation that atherogenesis is more pronounced in males. Compliance was proven by physical records of food consumption and by measured changes in w3 fatty acid content of tissues. Results did not provide any evidence that the fish oil was anti-atherogenic. The therapeutic diet effectively reversed lipid infiltration into arteries, as indicated previously by the prudent diet, but again components of advanced atherosclerosis such as cholesterol crystals, calcification and fibrosis did not regress in 20 months. There was minimal cerebral atherosclerosis, possibly because the walls of cerebral arteries are thin, almost like veins, which minimises tissue available for lipid accumulation. This suggests that the main pathogenesis of infarctive stroke may be by occlusive embolisation from carotid thrombi.

Summary and conclusions

The African Green monkey (Cercopithecus aethiops) has proven to be a suitable model for studying the effects of a variety of dietary components on plasma lipoprotein metabolism and atherosclerosis against a background of a Western atherogenic or prudent diet. The diets used in our studies were realistic, formulated entirely from cooked foods that are normal components of the diet of Westernised people with no extra synthetic cholesterol added. Very often diets are loaded with synthetic cholesterol and saturated fat, on the pretext of speeding up results. Our own results confirmed that this practice will almost invariably result in packing of cholesteryl esters into cores of enlarged LDL particles. This method is fundamentally flawed and is not a valid model for human atherosclerosis. It has been strongly criticised by pathologists^32,33. In contrast, experience with realistic diets showed LDL particles of relatively normal composition to also be atherogenic¹³. Models of human atherosclerosis Types I-VII^32,33, as defined by anatomical, cellular and extracellular criteria, have been achieved by our methods^1,15,17. Duration of exposure to a natural ingredient atherogenic diet should, however, be at least three years in adult males and four years in adult females. Individuals allocated to treatments should further be matched for sex, age, and plasma lipids^1,15,17,20. Experience also showed that it is important to use untreated reference controls to check for effects not due to treatments or sampling error such as stress and subclinical disease^1,12,17,20.

Dietary manipulation in the African Green monkey is simple, relatively inexpensive and offers almost unlimited options for dietary intervention studies.

---

References

1. Fincham JE, Woodroof CW, van Wyk MJ, Capatos D, Weight MJ, Kritchevsky D, Rossouw JE. Promotion and regression of atherosclerosis in Vervet monkeys by diets realistic for Westernised people. Atherosclerosis 1987; 66: 205-213.
2. Faggiotto A, Ross R, Harker L. Studies of hypercholesterolaemia in the nonhuman primate. I. Changes that lead to fatty acid streak formation. Arteriosclerosis 1984; 4: 323-340.
3. Parks JS, Lehner NDM, St Clair RW, Lofland HB. Whole body cholesterol metabolism in cholesterol-fed African Green monkeys with a variable hypercholesterolaemic response. J Lab Clin Med 1977; 90: 1021-1034.
4. Baker HN, Eggen DA, Melchior GW, Roheim PS, Malcolm GT, Strong JP. Lipoprotein profiles in Rhesus monkeys with divergent responses to dietary cholesterol. Arteriosclerosis 1983; 3: 223-232.
5. Wissler RW, Vesselinovitch D, Hughes R, Turner D, Frazier L. Arterial lesions and blood lipids in Rhesus monkeys fed human diets. Exp Mol Pathol 1983; 38: 117-136.
6. Hoover GA, Nicolosi RJ, Camp RR, Hayes KC. Characteristics of aortic intima in young and old Cebus and Squirrel monkeys. Arteriosclerosis 1982; 2: 252-265.
7. Joniken MP, Clarkson JB, Pritchard RW. Recent advances in molecular pathology: animal models in atherosclerosis. Exp Mol Pathol 1985; 42: 1-28.
8. Rudel LL, Leathers CW, Bond MG, Bullock BC. Dietary ethanol-induced modifications in hyperlipoproteinaemia and atherosclerosis in nonhuman primates (Macaca Nemestrina). Arteriosclerosis 1981; 1: 144-155.
9. Rudel LL, Bond MG, Bullock BC. LDL heterogenecity and atherosclerosis in non-human primates. Ann NY Acad Sci 1985; 454: 248-253.
10. Melchior GW, Rudel LL. Heterogenecity in the low density lipoproteins of cholesterol-fed African Green monkey (Cercopithecus aethiops). Biochim Biophys Acta 1978; 531: 331-343.
11. Weight MJ, Benadé AJS, Lombard CJ, Fincham JE, Marais M, Dando B, Seier JV, Kritchevsky D. Low density lipoprotein kinetics in African Green monkeys showing variable cholesterolaemic responses to diets realistic for westernised people. Atherosclerosis 1988; 73: 1-11.
12. Kruger M, Smuts CM, Benadé AJS, Fincham JE, Lombard CJ, Albertse EA, van der Merwe KJ. Comparison of the effect of the amount and degree of unsaturation of dietary fat on plasma low density lipoprotein in Vervet monkeys. Lipids 1992; 27: 733-739.
13. Benadé AJS, Fincham JE, Smuts CM, Lai Tung MT, Chalton D, Kruger M, Weight MJ, Daubitzer AK, Tichelaar HY. Plasma low density lipoprotein composition in relation to atherosclerosis in nutritionally defined Vervet monkeys. Atherosclerosis 1988; 74: 157-158.
14. Parks JS, Kaduck-Sawyer J, Bullock BC, Rudel LL. Effect of dietary fish oil on coronary artery and aortic atherosclerosis in African Green monkeys. Atherosclerosis 1990; 10: 1102-1112.
15. Fincham JE, Gouws E, Woodroof CW, van Wyk MJ, Kruger M, Smuts CM, van Jaarsveld PJ, Taljaard JJF, Schall R, Strauss JAdeW, Benadé AJS. Chronic effects of fish oil and a therapeutic diet in nonhuman primates. Arteriosclerosis and Thrombosis 1991; 11: 719-732.
16. Smuts CM, Kruger M, van Jaarsveld PJ, Fincham JE, Schall R, van der Merwe KJ, Benadé AJS. The influence of fish oil supplementation on plasma lipoproteins and arterial lipids in Vervet monkeys with established atherosclerosis. Prostaglandins Leukot Essent Fatty Acids 1992; 47: 129-138.
17. Fincham JE, Quack G, Wülfroth P, Benadé AJS. Confirmation of efficacy of etofibrate against peripheral atherosclerosis in non-human primates which model human lesion types I-VII. Drug Research 1996; 46: 519-525.
18. Fincham JE, Jooste PL, Seier JV, Taljaard JJF, Weight MJ, Tichelaar HY. Ethanol drinking by Vervet monkeys (Cercopithecus pygerethrus): individual responses of juvenile and adult males. J Med Primatol 1986; 15: 183-197.
19. Seier JV. Breeding Vervet monkeys (Cercopithecus pygerethrus) in a closed environment. J Med Primatol 1986; 15: 339-349.
20. Fincham JE, Faber M, Weight MJ, Labadarios D, Taljaard JJF, Steytler JG, Jacobs P, Kritchevsky D. Diets realistic for westernised people significantly effect lipoproteins, calcium, zinc, vitamins C, E, B₆ and haematology in Vervet monkeys. Atherosclerosis 1987; 66: 191-203.
21. Lippel K, Gianturco S, Fogelman A, Nestel P, Grundy SM, Fisher W, Chait A, Albers J, Roheim PS. Lipoprotein heterogeneity workshop. Arteriosclerosis 1987; 7: 315-323.
22. Tall AR, Small DM, Atkinson D, Rudel LL. Studies on the structure of low density lipoproteins isolated from Macaca fascicularis fed an atherogenic diet. J Clin Invest 1978; 62: 1354-1363.
23. St Clair RW, Greenspan P, Leight M. Enhanced cholesterol delivery to cells in culture by low density lipoproteins from hypercholesterolemic monkeys: correlation of cellular cholesterol accumulation with low density lipoprotein molecular weight. Arteriosclerosis 1983; 3: 77-86.
24. Rudel LL, Reynolds JA, Bullock BC. Nutritional effects on blood lipid and HDL cholesterol concentrations in two subspecies of African Green monkeys (Cercopithecus aethiops). J Lipid Res 1981; 22: 278-286.
25. Davis HR, Bridenstine RT, Vesselinovitch D, Wissler RW. Fish oil inhibits development of atherosclerosis in Rhesus monkeys. Arteriosclerosis 1987; 7: 441-449.
26. Harris WS. Fish oils and plasma lipid and lipoprotein metabolism in humans: a critical review. J Lipid Res 1989; 30: 785-807.
27. Van Rooyen J. The effect of diet on the metabolism of n-6 and n-3 fatty acid in African Vervet monkeys. PhD dissertation, University of Stellenbosch, South Africa; 1993.
28. Malan MM. The effect of cholesterol and type of fat in the diet on the LDL composition of the African green monkey (Cercopithecus aethiops). Master thesis, University of Stellenbosch, South Africa; 1990.
29. Kotzé HF, van Wyk V, Fincham JE, Kruger M, Roodt JP, Badenhorst PN. Changes in platelet function in atherosclerotic Vervet monkeys after long term dietary enrichment with n-3 and n-6 essential fatty acids. Cardiovascular J Southern Afr 1995; 6: 211-217.
30. Wolfe MS, Parks JS, Morgan TM, Rudel LL. Childhood consumption of polyunsaturated fat lowers risk of coronary artery atherosclerosis in African Green monkeys. Atherosclerosis and Thrombosis 1993; 13: 863-875.
31. Venter FS, Cloete H, Seier JV, Faber M, Fincham JE. Folic acid and vitamin B₁₂ status of Vervet monkeys used for nutritional research. Laboratory Animals 1993; 27: 59-64.
32. Stary HC. Composition and classification of human atherosclerotic lesions. Virchows Archives A Pathol Anat 1992; 421: 277-290.
33. Stary HC, Chandler B, Glagov S, Guyton JR, Insull W, Rosenfeld ME, Schaffer MA, Schartz CJ, Wagner WD, Wisseler RW. A definition of initial, fatty streak and intermediate lesions of atherosclerosis. Arteriosclerosis and Thrombosis 1994; 14: 840-856.

---

Vervet monkeys and whole-food diets for studying the effects of dietary lipids on plasma lipoprotein metabolism and atherosclerosis
AJS Benadé, JE Fincham, CM Smuts, MJ Weight, PJ van Jaarsveld, M Kruger
Asia Pacific Journal of Clinical Nutrition (1997) Volume 6, Number 1: 17-21

Copyright © 1993 [Asia Pacific Journal of Clinical Nutrition]. All rights reserved.

to the top