Dietary α-Lipoic Acid Supplementation Inhibits Atherosclerotic Lesion Development in Apolipoprotein E–Deficient and Apolipoprotein E/Low-Density Lipoprotein Receptor–Deficient Mice

Abstract

Background-Vascular inflammation and lipid deposition are prominent features of atherosclerotic lesion formation. We have shown previously that the dithiol compound ␣-lipoic acid (LA) exerts antiinflammatory effects by inhibiting tumor necrosis factor-␣-and lipopolysaccharide-induced endothelial and monocyte activation in vitro and lipopolysaccharide-induced acute inflammatory responses in vivo. Here, we investigated whether LA inhibits atherosclerosis in apolipoprotein E-deficient (apoE Ϫ/Ϫ ) and apoE/low-density lipoprotein receptor-deficient mice, 2 well-established animal models of human atherosclerosis. Methods and Results-Four-week-old female apoEϪ/Ϫ mice (nϭ20 per group) or apoE/low-density lipoprotein receptor-deficient mice (nϭ21 per group) were fed for 10 weeks a Western-type chow diet containing 15% fat and 0.125% cholesterol without or with 0.2% (wt/wt) R,S-LA or a normal chow diet containing 4% fat without or with 0.2% (wt/wt) R-LA, respectively. Supplementation with LA significantly reduced atherosclerotic lesion formation in the aortic sinus of both mouse models by Ϸ20% and in the aortic arch and thoracic aorta of apoE Ϫ/Ϫ and apoE/low-density lipoprotein receptor-deficient mice by Ϸ55% and 40%, respectively. This strong antiatherogenic effect of LA was associated with almost 40% less body weight gain and lower serum and very low-density lipoprotein levels of triglycerides but not cholesterol. In addition, LA supplementation reduced aortic expression of adhesion molecules and proinflammatory cytokines and aortic macrophage accumulation. These antiinflammatory effects of LA were more pronounced in the aortic arch and the thoracic aorta than in the aortic sinus, reflecting the corresponding reductions in atherosclerosis. Conclusions-Our study shows that dietary LA supplementation inhibits atherosclerotic lesion formation in 2 mouse models of human atherosclerosis, an inhibition that appears to be due to the "antiobesity," antihypertriglyceridemic, and antiinflammatory effects of LA. LA may be a useful adjunct in the prevention and treatment of atherosclerotic vascular diseases. (Circulation. 2008;117:421-428.)

R-α-lipoic acid does not reverse hepatic inflammation of aging, but lowers lipid anabolism, while accentuating circadian rhythm transcript profiles

“…Because of the particular cellular pathways influenced by orally administered LA, this compound is now under active consideration as a clinical adjunct for the treatment of diverse pathologies such as hypertension (31), atherosclerosis (59), proinflammatory conditions (23,47), hypertriglyceridemia (3), and diabetes-induced polyneuropathies (43,62). However, it is still unknown whether LA supplementation given over days or weeks at doses appropriate for pharmacological intervention would instigate similar or altogether distinct effects compared with those achieved by acute LA treatment.…”

Oral administration of alkaloid fraction fromRuta graveolensinhibits oxidative stress and inflammation in hypercholesterolemic rabbits

“…Epidemiological investigation revealed a positive correlation between the severe degree of atherosclerosis and the concentrations of plasma cholesterol as well as LDL (Goldstein et al, 1973;Zhang et al, 2008). After the intake of atherogenic diet that contained high cholesterol, a significant increase of different plasma lipids such as TC and LDL-C with a parallel decrease in HDL was observed compared with that of control group.…”

Pencegahan Lesi Aterosklerosis Oleh Asam Alfa Lipoat Pada Aorta Mencit Jantan (Mus Musculus) Yang Diberi Diet Tinggi Kolesterol

“…Asam alfa lipoat juga mensupresi ekspresi CAM sehingga mencegah selsel darah putih (granulosit, monosit dan limfosit) menempel pada dinding pembuluh darah. 15,17 Adanya pengurangan pembentukan lesi aterosklerosis pada aorta mencit pada penelitian ini juga dapat dihubungkan dengan penurunan kadar kolesterol pada plasma mencit maupun penurunan kadar MDA pada plasma mencit. Asam alfa lipoat dapat menurunkan kadar kolesterol total darah melalui pengaturan aktivitas enzim yang berperan dalam metabolisme kolesterol.…”