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

Christopher Ballmann, Thomas S. Denney, Ronald J. Beyers, Tiffany Quindry, Matthew Romero, Rajesh Amin, Joshua T. Selsby, John C. Quindry

Research output: Contribution to journalArticlepeer-review

Abstract

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 mo, Mdx/Utrn+/-mice were fed quercetin-enriched (Mdx/Utrn+/--Q) or control diet (Mdx/Utrn+/-) for 8 mo. Control C57BL/10 (C57) animals were fed a control diet for 10 mo. Cardiac function was quantified by MRI at 2 and 10 mo. Spontaneous physical activity was quantified during the last week of treatment. At 10 mo hearts were excised for histological and biochemical analysis. Quercetin feeding improved various physiological indexes 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 colocalization of utrophin and α-sarcoglycan. Lower abundance of fibronectin, cardiac damage (Hematoxylin Eosin-Y), and MMP9 were observed in quercetin-fed vs. control Mdx/Utrn+/- mice. Quercetin evoked higher protein abundance of PGC-1α, cytochrome c, ETC complexes I-V, citrate synthase, SOD2, and GPX compared with control-fed Mdx/Utrn+/-. Quercetin decreased abundance of inflammatory markers including NFKB, TGF-β1, and F4/80 compared with Mdx/Utrn+/-; however, P-NFKB, P-IKBα, IKBα, CD64, and COX2 were similar between groups. Dietary quercetin enrichment improves cardiac function in aged Mdx/Utrn+/- mice and 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.

Original languageEnglish
Pages (from-to)H128-H140
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume312
Issue number1
DOIs
StatePublished - 2017

Keywords

  • Duchenne muscular dystrophy
  • Polyphenol
  • Utrophin

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