Abstract 13895: Modulation of microRNA 15b and Its Downstream Protein Targets in the Heart by Oral Ingestion of Beetroot Juice: Potential Protective Role against Doxorubicin Cardiotoxicity
Background: Beetroot juice (BRJ) is a natural food product containing high levels of nitrate and antioxidant flavonoids/vitamins. Oral intake of BRJ protects against cardiotoxicity of doxorubicin (DOX) - an anticancer drug. BRJ reduced serum cardiac troponin I and ventricular dysfunction caused by DOX and increased plasma nitric oxide (NO) levels. The present study aims at elucidating the effects of BRJ on microRNA 15b (miR15b) - a key modulator of cellular bioenergetics and survival pathways and play an important role in cardiac ischemia-reperfusion injury.
Methods & Results: Adult male CF-1 mice were divided into 4 groups (n=3-4/group): 1) Saline [0.2 ml, IP]; 2) DOX [15 mg/kg, IP]; 3) BRJ [BRJ extract added in drinking water (10 g/L) for 13 days]; 4) BRJ+DOX - mice ingested BRJ for 7 days before DOX injection and through the 5-day post-DOX period. Five days after DOX or saline injection, ventricular tissues were collected for real-time PCR or Western blot assays. miR15b expression was significantly decreased in DOX-treated hearts (Fig. A). BRJ intake not only enhanced the basal level of miR15b, but also completely prevented the depressive effects of DOX on miR15b. BRJ also significantly reduced the protein targets of miR15b - Bcl-2, but not Arl2 (ADP-ribosylation factor-like protein 2) and ANT1 (ADP/ATP translocase 1) (Fig. B, C). Interestingly, we also observed inhibitory effects of BRJ on Bax and NOSTRIN (endothelial nitric oxide synthase traffic inducer) (P<0.05), indicating its potential modulation on eNOS activity and NO production (Fig. B, C).
Conclusion: Oral ingestion of BRJ significantly enhanced miR15b expression in the heart, which is associated with down-regulation of several protein targets that may act in concert to affect the crucial cellular bioenergetics and survival processes deranged by DOX. These novel findings may help to understand the cardioprotective mechanisms of BRJ as an effective and safe dietary supplement in combating DOX cardiotoxicity.
- © 2013 by American Heart Association, Inc.