Atherosclerosis animal studies

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... 

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... 

Finally, creatine supplements may be useful in the treatment of heart problems. Creatine has improved exercise capacity in patients suffering from congestive heart failure, and lowered blood cholesterol in animal studies. Limited study of creatine s effect on blood cholesterol levels in healthy humans has had mixed results, with one study reporting a positive impact and another reporting no effect at all. Further research is needed to determine if creatine is beneficial in improving blood cholesterol and preventing atherosclerosis. 

The noninvasive demonstration that lowering plasma cholesterol sufficiently results in either regression or lack of progression of atherosclerosis in man (and the very large amount of evidence to support this from animal studies) leads one to expect that direct evidence can be obtained that choles-... 

Nevertheless, the summary of the proceedings [137] of a National Heart, Lung, and Blood Institute workshop September 5-6, 1991, Bethesda, MD, entitled Antioxidants in the prevention of human atherosclerosis will serve as a conclusion "More Basic Research is needed on the mechanisms involved in the oxidative modification of LDL and on the ways in which various antioxidants influence it and More animal studies are needed to establish firmly that protection of LDL against oxidative modification does influence the progression of lesions . 

Direct proof of a protective effect of exercise on the development of atherosclerosis in humans is lacking. To date, only a few animal studies have provided strong evidence in favor of a beneficial effect of exercise on diet-induced atherogenesis (79,80). 

An abnormal lipoprotein profile increases the risk of atherosclerosis and coronary heart disease in patients with nephrotic syndrome. It is therefore prudent to treat patients with persistent nephrotic syndrome and sustained dyshpidemia, especially those with high VLDL and LDL cholesterol levels in the presence of a normal or low HDL cholesterol level (see Chaps. 21 and 43). Therapy is especially needed for those with concurrent atherosclerotic cardiovascular disease, or with additional risk factors for atherosclerosis, such as smoking and hypertension. Whether correction of hpoprotein abnormahties will slow the progression of renal disease as demonstrated in animal studies requires clinical confirmation. ... 

Meagher, E. and Rader, D.J. Antioxidant therapy and atherosclerosis Animal and human studies. Trends Cardiovasc Med. 11, 162-165 (2001). 

A. niger CGC has been shown to prevent the early development of atherosclerosis in an in-vivo animal study [190], In that study, Syrian golden hamsters were fed with a hyperlipidic diet and the test animal group received a daily dose of CGC. The results showed that CGC did not affect plasma cholesterol but lowered triglycerides, reduced the aortic fatty streak accumulation and improved the antioxidant status. 

The potency of antioxidants to inhibit LDL oxidation in vitro does not correlate with their potency to reduce atherosclerosis in vivo. If functions of antioxidants are due to the protection of LDL from oxidation, water-soluble antioxidants, which are unable to adhere to LDL, may be disadvantageous to protect LDL from oxidation in the subendothelial space. However, epidemiological and animal studies have shown that maiQr water-solifole antioxidants, such as flavonoids, reduce atherosclerosis (5). It is likely that water-soluble antioxidants reduce atherosclerosis by preventing the loss of endogenous lipophilic antioxidants in LDL (mainly a-tocopherol) (11,12). These antioxidants may also prevent endothelial injury causing dyslipidemia and oxidative stress in the circulation. 

There is accumulating evidence from animal studies that CLA has potential health benefits for humans (Sebedio et al., 1999 Roche et al., 2001). Potential anti-cancer properties of CLA have been reported using rodent mammary and colon cancer models (see Sebedio et al., 1999). Potential beneficial effects of CLA on body composition (i.e. reduced fat mass) have been reported in rodents, chickens and pigs (see Sebedio et al., 1999 Roche et al., 2001). Effects of CLA on plasma triacylglycerol concentration, on glucose homeostasis, on atherosclerosis, and on inunune function have also been reported in animal studies (see Sebedio et al., 1999 Roche et al., 2001). Many of these animal studies have used a mix of CLA isomers, but predominantly the cis 9, trans 11... 

Oxidation of LDL plays an important role in the development of atherosclerosis. Turmeric extract decreased the susceptibility of LDL to lipid peroxidation, thus suggesting its value in the management of cardiovascular disease (Ramirez-Tortosa et al. 1999). In healthy hiunans, the daily intake of 200 mg of turmeric extract resulted in a decrease in total blood lipid peroxides as well as in HDL- and LDL-lipid peroxidation (Miquel et al. 2002). The beneficial influence of dietary curciunin on the susceptibility of LDL to oxidation was examined in an animal study. Dietary curcumin significantly inhibited the in vivo iron-induced LDL oxidation as well as copper-induced oxidation of LDL in vitro (Manjunatha and Srinivasan 2006). 

Documenting the sequence of events in the pathogenesis of any human disease is difficult because the early phases of the disease often go undetected and the disease is only recognized when clinical symptoms appear. Thus, the bulk of information that is available on the pathogenesis of atherosclerosis is derived from animal studies in which initiating events can be controlled and subsequent events closely... 

The type of protein in the diet also influences cholesterolemia and atherosclerosis. In animal studies in which the sole source of protein is of animal or plant origin, the former is more cholesterolemic than atherogenic. However, a 1 1 mix of animal and plant protein provides the higher-grade protein of animal protein and the normocholesterolemic effects of plant protein. The results underline the need for a balanced diet. 

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). 

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