The Effect of Bisphenol A on the Atherosclerosis

Abstract

Introduction: There is growing concern about the association between human exposure to BPA and increased risk of cardiovascular disease in epidemiological studies. We investigated whether BPA can accerelate atherosclerosis using mouse model and what is its underlying mechanism.

Methods: Apolipoprotein E knockout (ApoE-/-) mice were fed a high-fat and high-cholesterol diet with or without 50 μg/kg bw/day of BPA for 12 weeks. Atherosclerotic lesions of aorta and aortic sinus were evaluated with Oil red O stain and macrophages in the atherosclerotic plaque were stained with anti-F4/80 antibody. To determine that oxidative stress is involved in the development of atherosclerosis, we supplemented α-lipoic acid (LA) concomitantly with BPA. We measured the malondialdehyde (MDA) concentration and stained with dichlorodihydrofluorescein (DCF) after 0.1 nM – 10 nM of BPA treatment in human umbilical vein endothelial cells (HUVEC).

Results: Atherosclerotic lesions of aorta in the BPA group was larger compared to the control group (9.7 ± 1.8% vs. 4.3 ± 1.0%, p = 0.02) in ApoE-/- mice. BPA increased the infiltration of macrophages in atherosclerotic plaques of aortic sinus. Serum TNF-α and IL-6 levels showed a tendency to increase in the BPA group compared to the control group. When LA was treated concomitantly wtih BPA, atheroscleric lesions and the infiltration of macrophages decreased. In HUVEC, BPA increased MDA concentration and fluorescence after DCF staining. LA supplement with BPA recovered both of them.

Conclusions: BPA accelerated atherosclerosis in ApoE-/- mice. An increase of inflammation and oxidative stress by BPA could be one of possible mechanisms of BPA-induced atherosclerosis.