PGz Reverses Cardiac Dysfunction in Dystrophic Mice

Abstract

Duchenne muscular dystrophy (DMD) is caused by the absence of dystrophin expression and is one of the most common genetic diseases of children worldwide. Duchenne cardiomyopathy (D-CM) is observed in all patients suffering from DMD as the disease progresses. Despite knowing the cause of DMD and D-CM, there are no treatments which reverse its inevitable progression.Periodic Acceleration (pGz) is a novel method that applies repetitive, sinusoidal, head-to-foot motion to a horizontally positioned body to induce increased pulsatile shear stress in fluid channels throughout the entire body. pGz increases the expression of eNOS, and nNOS and other endothelial derived proteins. Experiments were conducted in cardiomyocytes isolated from Wt and mdx mice (3, 6, 9 and 12-mo), treated or not with pGz (one hour for 16 consecutive days). Resting Ca2+ ([Ca2+]r) and Na+ ([Na+]r) were determined using Ca2+ and Na+ selective microelectrodes. pGz did not modify [Ca2+]r or [Na+]r in cardiomyocytes from Wt mice at any age (3, 6, 9 and 12-mo). In contrast, pGz restored [Ca2+]r and [Na+]r to Wt levels in cardiomyocytes from 3, 6 and 9-mo mdx mice and significantly reduced [Ca2+]r and [Na+]r in those from 12-mo old mdx mice. To assess the [NO]i Wt and mdx cardiomyocytes isolated from mice of 3, 6, 9 and 12-mo of age were loaded with 10µM DAF-FM DA (Molecular Probes, OR, USA). pGz did not significantly modify DAF fluorescence in Wt cardiomyocytes at any age. In contrast, pGz reduced DAF-Fluorescence in treated mdx cardiomyocytes at 3,6, 9 and 12 mo of age compared to untreated mdx cardiomyocytes of the same age. Our results suggest that pGz can be a drug free therapeutic approach to treat the cardiomyopathy observed in patients suffering from D-CM.