Lifelong quercetin enrichment and cardioprotection in Mdx/Utrn+/− mice

Ballmann, Christopher
Denney, Thomas
Selsby, Joshua
Beyers, Ronald
Quindry, Tiffany
Romero, Matthew
Amin, Rajesh
Selsby, Joshua
Quindry, John
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Duchenne Muscular Dystrophy (DMD) is associated with progressive cardiac pathology, however, the SIRT1/PGC1-α activator quercetin may cardioprotect dystrophic hearts. We tested the extent to which long term 0.2% dietary quercetin enrichment attenuates dystrophic cardiopathology in Mdx/Utrn+/- mice. At 2 months, Mdx/Utrn+/- mice were fed quercetin enriched (Mdx/Utrn+/--Q) or control diet (Mdx/Utrn+/-) for 8 months. Control C57BL/10 (C57) animals were fed a control diet for 10 months. Cardiac function was quantified by MRI at 2 and 10 months. Spontaneous physical activity was quantified during the last week of treatment. At 10 months hearts were excised for histological and biochemical analysis. Quercetin feeding improved various physiologic indices of cardiac function in diseased animals. Mdx/Utrn+/--Q also engaged in more high intensity physical activity than controls. Histological analyses of heart tissues revealed higher expression and co-localization of utrophin and α-sarcoglycan. Lower abundance of fibronectin, cardiac damage (Hematoxylin Eosin-Y), and MMP9 were observed in quercetin fed versus control Mdx/Utrn+/- mice. Quercetin evoked higher protein abundance of PGC-1α, cytochrome-c, ETC complexes I-V, citrate synthase, SOD2, and GPX compared to control-fed Mdx/Utrn+/-. Quercetin decreased abundance of inflammatory markers including NFκB, TGF-β1, and F4/80 compared to Mdx/Utrn+/-, however, P-NFκB, P-IKBα, IKBα, CD64 and COX2 were similar between groups. Dietary quercetin enrichment improves cardiac function in aged Mdx/Utrn+/- mice, increases mitochondrial protein content, and dystrophin glycoprotein complex formation. Histological analyses indicate a marked attenuation in pathological cardiac remodeling and indicate that long term quercetin consumption benefits the dystrophic heart.


This is a manuscript of an article published as Ballmann, Christopher, Thomas S. Denney, Ronald J. Beyers, Tiffany Quindry, Matthew Romero, Rajesh Amin, Joshua T. Selsby, and John C. Quindry. "Lifelong quercetin enrichment and cardioprotection in Mdx/Utrn+/− mice." American Journal of Physiology-Heart and Circulatory Physiology 312, no. 1 (2017): H128-H140. doi: 10.1152/ajpheart.00552.2016. Posted with permission.