Beta-carotene inhibits atherosclerosis in hypercholesterolemic rabbits

Area of Science:

• Cardiovascular Research
• Nutritional Science
• Oxidative Stress Biology

Background:

• Oxidatively damaged low-density lipoprotein (LDL) is implicated in atherosclerosis.
• Epidemiological studies suggest dietary vitamin E and beta-carotene may reduce atherosclerotic vascular disease risk.
• This suggests lipid-soluble antioxidants might protect LDL from oxidation, thereby slowing disease progression.

Purpose of the Study:

• To investigate the effects of probucol, vitamin E, and beta-carotene isomers on LDL oxidation and atherosclerosis in rabbits.
• To determine if antioxidant protection of LDL correlates with inhibition of vascular disease.
• To explore potential mechanisms by which beta-carotene may affect atherogenesis.

Main Methods:

• Male New Zealand White rabbits were fed a high-cholesterol diet supplemented with probucol, vitamin E, all-trans beta-carotene, or 9-cis beta-carotene.
• LDL oxidation susceptibility was assessed ex vivo.
• Aortic atherosclerosis extent was quantified.

Main Results:

• Probucol inhibited LDL oxidation and atherosclerosis, consistent with prior studies.
• Vitamin E showed modest inhibition of LDL oxidation but did not prevent atherosclerosis.
• All-trans beta-carotene inhibited lesion formation similarly to probucol, despite not being detected in LDL and having no ex vivo LDL oxidation inhibitory effect. Tissue levels of retinyl palmitate increased.
• 9-cis beta-carotene had no significant effect on LDL oxidation or atherosclerosis.

Conclusions:

• The atheroprotective effect of all-trans beta-carotene is separable from its direct impact on LDL oxidation.
• Metabolites of all-trans beta-carotene may inhibit atherosclerosis in hypercholesterolemic rabbits.
• These effects might involve stereospecific interactions with retinoic acid receptors in the artery wall, rather than solely acting as an LDL antioxidant.