Animal models of atherosclerosis

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... 

Protein kinase C (PKC) is a family of enzymes that plays a major role in cell signaling and the modulation of gene expression related to cell growth, proliferation, and differentiation. PKC activation may also play a critical role in tumor promotion in some types of cancer. a-Tocopherol has been found to inhibit PKCa activity in a number of cell types and in animal models of atherosclerosis. PKCa inhibition by a-tocopherol appears umelated to its antioxidant function rather, oc-tocopherol may inhibit PKCa activity by promoting its dephosphorylation or by modulating diacylglycerol kirrase activity. ... 

Proof-of-principle studies using protein antagonists such as met-CCL5 have shown that inhibition of chemokine receptors improves outcome in animal models of atherosclerosis, graft rejection, and viral infection (Bonville et al, 2004 Veillard et al, 2004 Yun et al, 2004). Blockade of ehemokine funetion has also been explored as a strategy to treat inflammatory diseases like asthma, arthritis, and multiple sclerosis in animal models of disease. The... 

In an animal model of atherosclerosis E2 restores FasL expression, which is suppressed by atherogenic levels of serum cholesterol (328). High levels of Hey diminish with estrogen (reviewed in ref. 329). In HUVEC, E2 caused a decrease in expression of the NADPH oxidase subunit gp91phox, up-regulated eNOS expression, and inhibited the increase in adhesion molecule and chemokine expression in cells exposed to cyclic strain. Cyclic strain enhanced endothelial 02 formation, thereby offsetting the inhibitory effect of NO on the expression of these gene products (330). 

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. 

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). 

The consequence of inhibiting intestinal cholesterol absorption is a reduction in the incorporation of cholesterol into chylomicrons. The reduced cholesterol content of chylomicrons diminishes the dehvery of cholesterol to the hver by chylomicron remnants. The diminished remnant cholesterol content may decrease atherogenesis directly, as chylomicron remnants are very atherogenic hpoproteins. hi experimental animal models of remnant dyslipidemia, ezetimibe profoundly diminished diet-induced atherosclerosis. 

The association between atherosclerosis in humans and plasma lipoproteins has led to the development and use of several animal models to help our understanding of familial hypercholesterolemias and atherosclerosis however, the species differences in lipoproteins and their metabolism must be considered when developing models of atherosclerosis and novel therapeutic agents. Dietary manipulations in animals with dominant LDL-C fractions are perhaps more appropriate models for these studies than in animals where HDL is the dominant fraction (Cayen, Givner, and Kraml... 

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