Cardiac function in muscular dystrophy associates with abdominal muscle pathology

Abstract

Background The muscular dystrophies target muscle groups differentially. In mouse models of muscular dystrophy, notably the mdx model of Duchenne Muscular Dystrophy, the diaphragm muscle shows marked fibrosis and at an earlier age than other muscle groups, more reflective of the histopathology seen in human muscular dystrophy. Methods Using a mouse model of limb girdle muscular dystrophy, the Sgcg mouse, we compared muscle pathology across different muscle groups and heart. A cohort of nearly 200 Sgcg mice were studied using multiple measures of pathology including echocardiography, Evans blue dye uptake and hydroxyproline content in multiple muscle groups. Spearman rank correlations were determined among echocardiographic and pathological parameters. Findings The abdominal muscles were found to have more fibrosis than other muscle groups, including the diaphragm muscle. The abdominal muscles also had more Evans blue dye uptake than other muscle groups. The amount of diaphragm fibrosis was found to correlate positively with fibrosis in the left ventricle, and abdominal muscle fibrosis correlated with impaired left ventricular function. Fibrosis in the abdominal muscles negatively correlated with fibrosis in the diaphragm and right ventricles. Together these data reflect the recruitment of abdominal muscles as respiratory muscles in muscular dystrophy, a finding consistent with data from human patients.

NFĸB signaling drives myocardial injury via CCR2+ macrophages in a preclinical model of arrhythmogenic cardiomyopathy

“…Therefore, these double mutant mice (i.e., Dsg2 mut/mut × IκBαΔN) express an ACM disease allele and a IκBαΔN isoform that is nonphosphorylatable at Ser32/36 and, thus, retains inactivated-NFĸB within the cytoplasm of cardiac myocytes ( 15 , 16 ). Areas of myocardial injury and cardiac myocyte death were identified by Evan’s blue staining, as previously described ( 17 ). We observed an accumulation of macrophages expressing Ccr2 adjacent to areas of myocardial injury in Dsg2 mut/mut hearts.…”

Muscle pathology associated with cardiac function in Duchenne muscular dystrophy

“…Dystrophin, the product of the DMD gene is presented in all types of muscle including skeletal, smooth, and cardiac muscle bers. [10] Sequence and association of the musclce brosis of the diffente muscle groups during the progression of the disease is not fully investigated. In our study, muscle brosis progressed from the abdominal muscles to the proximal extremity muscles, followed by the distal extremity muscles.…”

“…[8, 9] An animal study con rmed signi cant associations between respiratory and cardiac functions and myocardial brosis. [10] However, no study has examined the relationship between brosis of the respiratory and extremity muscles and cardiac dysfunction in human.…”

238th ENMC International Workshop: Updating management recommendations of cardiac dystrophinopathyHoofddorp, The Netherlands, 30 November - 2 December 2018

“…Prof E McNally discussed the longer and more variable clinical timeline in BMD and its differences from DMD, noting that cardiac involvement in BMD could be disproportionately severe even in patients with mild skeletal phenotypes [2][3][4][5][6] . She reviewed the limited literature on steroid use in BMD and discussed alternative steroid regimens that may have fewer side effects [7,8] .…”

“…Prof E McNally explained that intercostal, abdominal and diaphragmatic muscles are all involved in DMD. Effective noninvasive ventilation has been shown not only to improve overall survival in DMD but also to benefit cardiac function and performance [55,56] . Data from animal models of DMD supports a strong interplay between cardiac and pulmonary function and emphasises the importance of the secondary muscles of respiration, especially the abdominal muscles, in influencing cardiac function [5] .…”