Animal models atherosclerosis

Probucol. Probucol is an antioxidant that is effective in lowering LDL cholesterol. Whereas probucol was known to lower cholesterol after relatively simple clinical trials (160), its mechanism of action as an antioxidant in the treatment of atherosclerosis is quite novel. Probucol has been shown to have the abiUty to produce regression of atherosclerotic lesions in animal models (161). Probucol therefore represents a novel class of pharmaceutical agent for the treatment of atherosclerosis. This effect occurs mechanistically, in part, by preventing oxidation of LDL, a necessary step in foam cell formation. This antioxidant activity has been shown in laboratory experiments and its activity in lowering LDL cholesterol in human studies is well documented (162). 

Kita, T., Nagano, X., Yokode, M., Ishii, K., Kume, N., Ooshima, A., Yoshida, H. and Kawai, C. (1987). Probucol prevents the progression of atherosclerosis in Watanabe heritable hyperlipidaemic rabbits an animal model for hyper-cholesterolaemic. Proc. Natl Acad. Sci. USA 84, 5928-5931. 

Key Words Atherosclerosis chemokine chemokine receptor inflammation animal model CCR2 MCP-1 CX3CR1 fractalkine. 

Restenosis after angioplasty is a situation where these therapies may find an early application. The current animal models evaluate the formation of atherosclerosis or a neointima in the same accelerated and artificially induced... 

The disturbance of balance between superoxide and nitric oxide occurs in a variety of common disease states. For example, altered endothelium-dependent vascular relaxation due to a decrease in NO formation has been shown in animal models of hypertension, diabetes, cigarette smoking, and heart failure [21]. Miller et al. [22] suggested that a chronic animal model atherosclerosis closely resembles the severity of atherosclerosis in patients. On the whole, the results obtained in humans, for example, in hypertensive patients [23] correspond well to animal experiments. It is important that endothelium-dependent vascular relaxation in patients may be improved by ascorbic acid probably through the reaction with superoxide. 

The vascular wall is a target for sexual hormones. In the particular case of estrogens, specific receptors have been found in both endothelium and vascular smooth muscle cells (VSMC) (Venkov et al. 1996 Karas et al. 1994). The trophic effects of estrogens on the endothelium have been advocated as crucial against initiation and promotion of atherosclerosis. Thus, cellular and animal models,... 

ApoA-1 is the major structural lipoprotein component of HDL particles. Transgenic over-expression of apoA-1 has been well documented to correlate very strongly with antiatherogenic effects seen in a number of animal models [89-91]. The genetic deficiency of apoA-1 in humans has also been linked to low levels of HDL and premature atherosclerosis [90-92]. It is believed that infusion of apoA-1 enhances the ABCAl-mediated cholesterol efflux from macrophages [93]. During the last decade, significant efforts have been spent to find small... 

In animal models of atherosclerosis, vascular iron deposit is closely related to the progression of atherosclerosis and LDL oxidation, and restriction in dietary iron intake leads to significant inhibition of lesion formation (8), DFO forms a stable complex with ferric iron and decreases its availability for the production of reactive-oxygen species (28). Moreover, in high concentration (>0.5 mmol/L), DFO may also scavenge... 

As with atherosclerosis itself, recruitment of inflammatory cells is now recognized as an essential step in the pathogenesis of neointima formation in humans (I 1,12). In various animal models, reduction of leukocyte recruitment by selective blockade of adhesion molecules significantly reduced neointima formation and restenosis (13-16). Recent studies also concluded a role of pre-existing inflammation within the... 

B60. Buja, L. M., Kita, T., Goldstein, J. L., Watanabe, Y., and Brown, M. S., Cellular pathology of progressive atherosclerosis in the WHHL rabbit An animal model of familial hypercholesterolemia. Arteriosclerosis 3, 87-101 (1983). 

Ingestion of fenugreek powder reduces total cholesterol and triglyceride levels. Fenugreek is thus considered a dietary supplement for hyperlipidaemia and atherosclerosis in diabetic subjects (Sharma et al., 1996a). The antidiabetic effects of fenugreek seeds in type I and type II diabetes in both human and animal models have been well established (Basch et al, 2003). 

Several studies on animal models demonstrated that CLA could retard the development of atherosclerosis. The CLA used in these studies was a mixture of isomers in which RA and trans-10, cis- 2-Ci%a were predominant and present in near equal amounts. Because these two isomers can show identical biological effects in some tissues and dissimilar effects in other tissues, a benefit for RA in these studies cannot be assumed. Nevertheless, there is emerging evidence that RA has anti-atherogenic properties. 

Chapman KP, Stafford WW, Day CE (1976) Produced by selective breeding of Japanese quail animal model for experimental atherosclerosis. In Day CE (ed) Atherosclerosis Drug Discovery. Plenum Press, New York, London, pp 347-356... 

Day CE, Stafford WW (1975) New animal model for atherosclerosis research. In Kritchevsky D, Paoletti R, Holmes WL (eds) Lipids, Lipoproteins, and Drugs. Plenum Press, New York, pp 339-347... 

Day CE, Phillips WA, Schurr PE (1979) Animal models for an integrated approach to the pharmacologic control of atherosclerosis. Artery 5 90-109... 

Schafer HL, Linz W, Bube A et al. (1999) The Syrian hamster as animal model for atherosclerosis. Naunyn-Schmiedeberg s Arch Pharmacol 359S R111... 

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