Animal atherosclerosis

That being the case, one would expect reduction of blood pressure to be beneficial. It has been shown in experimental animals that animal atherosclerosis can go on at the same rate as in a normotensive animal if you make the animal hypertensive but keep his blood pressure from going up by giving him antihypertensive agents. 

Differences between human and animal atherosclerosis. Proceedings of the Third International Symposium on Atherosclerosis. 

Calcium Channel Blockers. Because accumulation of calcium is one of the facets of the mote involved process leading to atherosclerosis, it would foUow that the antihypertensive calcium channel blockers might be effective in preventing atheroma. Both verapamil (Table 1) and nifedipine (Table 3) have been shown to stimulate the low density Upoprotein (LDL) receptor (159). This specific receptor-mediated pathway could theoretically improve Upid metaboUsm in the arterial wall, and thereby prove antiatherogenic. These effects have been proven in animals. 

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). 

Cholesterol is a principal component of animal cell plasma membranes, and much smaller amounts of cholesterol are found in the membranes of intracellular organelles. The relatively rigid fused ring system of cholesterol and the weakly polar alcohol group at the C-3 position have important consequences for the properties of plasma membranes. Cholesterol is also a component of lipoprotein complexes in the blood, and it is one of the constituents oiplaques that form on arterial walls in atherosclerosis. 

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. 

Depletion of the antioxidant capacity of LDL is an early event in the oxidation process. The main antioxidant in LDL is a-tocopherol, with smaller quantities of 0-carotene and 7-tocopherol also present. The importance of antioxidants in inhibiting the oxidative modification of LDL is su ested by human and animal studies on the prevention of atherosclerosis. Preliminary reports... 

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

Molecule Cell expression Presumed role in atherosclerosis Animal data in atherosclerosis Human data in atherosclerosis... 

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... 

Our understanding of atherosclerosis as an inflammatory process has made great strides in the past decade, and it is clear from animal studies as well as clinical data that chemokines play an important role in atherosclerotic vascular... 

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,... 

Fig. 9.5. Protection by SERMs against atherosclerosis has been researched in animals. In a model of ovariectomized rabbits, raloxifene reduced the cholesterol content in the inner part of the aorta more than placebo did (upper panel). This effect was more intense in animals treated with estradiol (Bjarnason et al. 1997). In contrast, in a different model of oophorectomized monkeys (lower panel), estradiol, and not raloxifene at two different dosages, significantly decreased the size of atherosclerotic plaques (Clarkson et al. 1998)...

Cat K inhibitor therapy may also result in protection against the development of atherosclerosis. Cat K-deficient mice show reduced atherosclerotic lesion number and size on an ApoE receptor-deficient background, compared to wild-type animals [38,39]. Cat K is also associated with increased adiposity in humans [27,28] and may also play a role as a kininase, suggesting a role in blood pressure regulation [40]. Cat K has also been postulated to play a role in the pathology of rheumatoid arthritis [41,42],... 

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... 

Epileptiform fits associated with degenerative changes in the myelin sheath of peripheral nerves and spinal cord occur in B6-deficient animals. Lesions in the arteries, resembling those of human atherosclerosis, have been observed in Be-deficient monkeys. Recently, a state of Be deficiency in human infants, characterized by loss of ability to convert tryptophan to nicotinic acid, by impaired growth, convulsions, and hypochromic anemia, has been described, following omission of vitamin B6 from the diet. 

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