Food supplementation with rice bran enzymatic extract prevents vascular apoptosis and atherogenesis in ApoE−/− mice
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Atherosclerosis is associated with reduced mononuclear cell (MNC) telomere length, and senescent cells have been detected in atherosclerotic plaques. Rice bran is a source of γ-oryzanol, phytosterols and tocols with potential lipid-lowering, antioxidant and anti-inflammatory activities. Here, we tested the hypothesis that rice bran enzymatic extract (RBEE) impacts on apoptosis, telomere length and atherogenesis in mice.
Seven-week-old male ApoE−/− mice were fed high-fat diet (HFD) or isocaloric HFD supplemented with 5 % (w/w) RBEE for 23 weeks. Wild-type mice of the same age were kept under standard diet as controls.
RBEE treatment reduced total cholesterol (19.24 ± 1.63 vs 24.49 ± 1.71 mmol/L) and triglycerides (1.13 ± 0.18 vs 1.75 ± 0.22 mmol/L) and augmented HDL-cholesterol (1.86 ± 0.20 vs 1.07 ± 0.20 mmol/L). RBEE attenuated macrophage infiltration by 56.69 ± 4.65 % and plaque development (7737 ± 836 vs 12,040 ± 1001 μm2) in the aortic sinus. In the aorta, RBEE treatment reduced expression of the apoptosis pathway components p16, p53 and bax/bcl-2 ratio. RBEE prevented apoptosis of aortic endothelial cells (2.81 ± 0.71–1.14 ± 0.35 apoptotic nuclei/ring for ApoE−/− HFD and ApoE−/− HFD 5 % RBEE, respectively). In contrast, MNC of RBEE-fed mice exhibited enhanced apoptosis marker expression with increased p53 and bax/bcl-2 protein levels. Compared to WT, ApoE−/− mice on HFD were characterized by significant telomere shortening in aorta (11 ± 2 %) and MNC (73 ± 7 %), which was reduced by supplementation with RBEE (aorta: 40 ± 7 %; MNC: 105 ± 10 %). Expression of telomere repeat-binding factor 2 was increased in RBEE-fed mice.
Long-term food supplementation with RBEE lowers cholesterol and prevents atherosclerotic plaque development in ApoE−/− mice. Differential regulation of vascular and MNC apoptosis and senescence were identified as potential mechanisms.
KeywordsApoE−/− Rice bran enzymatic extract Atherosclerosis Inflammation Apoptosis Telomeres
The authors thank Dr. Juan Parrado (University of Seville) for supplying the rice bran extract (RBEE) and Jennifer Kieffer and Ellen Becker for excellent technical assistance. The study was funded by the Corona foundation via the Stifterverband für die Deutsche Wissenschaft and the Spanish Government. Cristina Perez-Ternero is a recipient of a FPU fellowship from the Spanish Government.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Approval for all experiments was provided by the Ethic Committee for Animal Experimentation of the University of Seville (Spain) (AGL2013-407791-P). The manuscript does not contain clinical studies or patient data.
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