Elsevier

Atherosclerosis

Volume 163, Issue 1, July 2002, Pages 79-87
Atherosclerosis

Taurine suppresses development of atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits

https://doi.org/10.1016/S0021-9150(01)00764-XGet rights and content

Abstract

While the hypocholesterolemic effects of taurine have extensively been studied using experimental animals, the anti-atherosclerotic effects of taurine have been given less attention. We examined the effect of taurine on atherosclerotic lesions in Watanabe heritable hyperlipidemic (WHHL) rabbits. Treatment of WHHL rabbits with taurine (0.3% in drinking tap water) for 24 weeks decreased aortic lesions by 31%, estimated as intimal thickening. Taurine significantly decreased cholesteryl ester content of aortic arch, thoracic aorta, and abdominal aorta by 35, 43, and 54%, respectively. Concomitantly, activity of acyl-CoA:cholesterol acyltransferase (ACAT), an enzyme responsible for cholesterol esterification, was also significantly decreased. Immunohistochemical analysis revealed decreased macrophages in the intima of taurine-treated rabbits. Taurine had no apparent effect on blood pressure and serum cholesterol levels. Contents of thiobarbituric acid reactive substances (TBARS), a marker of lipid peroxidation, was reduced in serum and aorta by 29 and 50%, respectively, when taurine was ingested. In addition, LDL from taurine-treated rabbits was resistant to copper-induced oxidative modification. These results revealed that taurine prevents development of atherosclerosis and that the anti-atherosclerotic effects of taurine are independent of serum cholesterol levels. The anti-oxidant action of taurine may be involved in inhibiting atherosclerosis in these rabbits.

Introduction

Taurine, a sulfur-containing amino acid, is widely distributed in animal tissues, and has a variety of physiological and pharmacological effects [1], [2], [3]. A worldwide epidemiological study, WHO-CARDIAC study, revealed a strong and inverse association between population levels of taurine excretion and ischemic heart disease mortality, and suggested that taurine intake is effective in preventing cardiovascular disease [4]. Numerous data suggest that taurine has beneficial effects on cholesterol metabolism, in relation to improvement in hypercholesterolemia [5], [6], [7], [8], [9]. As was shown in epidemiological studies, reduction in plasma atherogenic lipoproteins such as low density lipoprotein (LDL) and very low density lipoprotein (VLDL) is expected to prevent atherosclerosis and coronary heart disease [10]. However, there are few reports on effects of taurine on initiation and progression of atherosclerosis. Petty et al. [11] showed that taurine prevents the progression of atherosclerosis in rabbits fed a cholesterol-rich diet, without altering serum cholesterol. We noted that taurine decreases aortic lipid accumulation in C57BL/6J mice fed a high-fat diet [9] and in apolipoprotein E-deficient mice [12]. The Watanabe heritable hyperlipidemic (WHHL) rabbit carries an inheritable mutation of the LDL receptor, similar to that in cases of human familial hypercholesterolemia [13], [14]. The defective expression of LDL receptor results in the loss of high affinity absorption and degradation of LDL. The homozygous WHHL rabbit has severe hypercholesterolemia even from birth and develops atherosclerotic lesions with age. WHHL rabbit is therefore a useful model for assessing various therapeutic approaches for the prevention and treatment of atherosclerosis. Cholesterol-lowering and anti-atherosclerotic effects of compounds and drugs such as inhibitors of hydroxy-methylglutaryl CoA reductase [15], probucol [16], vitamin E [17], and fish oil [18] have been evaluated using this animal model. The objective of the present study was to determine the effect of long-term administration of taurine on serum cholesterol levels and on the progression of atherosclerosis.

Section snippets

Animals

Twelve male homozygous WHHL rabbits (2 months old) weighing 1.66–2.06 kg obtained from Kitayama Labes Co. (Ina, Japan), were housed individually under controlled environmental conditions (temperature 22±2 °C, humidity 60±15%, 12/12 h light–dark cycle, air changed 12 times/h) and were provided standard chow pellets (Oriental Yeast, Tokyo, Japan) throughout the experiment. For histological analysis, additional 12 male WHHL rabbits were used. Animals were divided into two groups (control and

Food and water consumption and body weight

There was no significant difference in food and water intake by the rabbits during the experiment. Based on water intake, the mean daily intake of taurine was 230 mg/kg. No adverse effect of taurine on the clinical appearance was observed in any rabbit and significant differences in body weight between the two groups were nil. The body weights for the control and taurine groups were 1.81±0.05 and 1.96±0.04 kg, respectively, at start of the experiment and were 3.70±0.08 and 3.96±0.12 kg,

Discussion

Our data show that taurine prevents the progression of atherosclerosis in WHHL rabbits. Petty et al. [11] showed that taurine suppresses atherosclerosis without affecting serum cholesterol levels in New Zealand white rabbits fed a cholesterol-rich diet. Although they speculated a possible involvement of anti-oxidant activity in anti-atheorsclerotic effects of taurine, they gave no clear experimental evidence. We found that taurine intake decreased TBARS level of serum and aorta, and that LDL

Acknowledgements

We thank Ryozi Hiraide of Kitayama Labes Co. for expertise in animal care.

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