Cardiac dysfunction is a primary cause of mortality in Duchenne Muscular Dystrophy (DMD), potentially related to elevated cytosolic calcium. However, the regional versus global functional consequences of cellular calcium mishandling have not been defined in the whole heart. Here, we elucidate, for the first time, loci- and age-dependencies between calcium mishandling and myocardial sheet function as a manifestation of dystrophin-deficient cardiomyopathy. We also map calcium transients to illustrate the regional dependence of ion flux disturbances in the dystrophin-deficient (mdx) mouse heart. Furthermore, we elucidate abnormalities in autophagic processes that can be corrected with nanoparticle therapeutics delivering rapamycin to heart tissues to improve ventricular function in affected older mice with incipient cardiomyopathy. We conclude that the rapid reversibility of functional defects by reducing cytosolic calcium or by impacting impaired autophagy points to the significance of regional mechanical factors in the progression of the disease.
","abstract_html":"<p>Cardiac dysfunction is a primary cause of mortality in Duchenne Muscular Dystrophy (DMD), potentially related to elevated cytosolic calcium. However, the regional versus global functional consequences of cellular calcium mishandling have not been defined in the whole heart. Here, we elucidate, for the first time, loci- and age-dependencies between calcium mishandling and myocardial sheet function as a manifestation of dystrophin-deficient cardiomyopathy. We also map calcium transients to illustrate the regional dependence of ion flux disturbances in the dystrophin-deficient (mdx) mouse heart. Furthermore, we elucidate abnormalities in autophagic processes that can be corrected with nanoparticle therapeutics delivering rapamycin to heart tissues to improve ventricular function in affected older mice with incipient cardiomyopathy. We conclude that the rapid reversibility of functional defects by reducing cytosolic calcium or by impacting impaired autophagy points to the significance of regional mechanical factors in the progression of the disease.</p>","abstract_has_math":false,"creators":["Cheng, Ya-Jian"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Biomedical Engineering","degree_department":null,"school":null,"contributors":["Samuel A. Wickline"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-02-17T08:00:00Z","date_published":"2014-02-17T08:00:00Z","updated_at":"2026-07-24T06:12:48Z","subjects":["Diffusion tensor MRI","Duchenne Muscular dystrophy","heart base","heart muscle sheet","mdx mouse","Biomedical Engineering and Bioengineering"],"languages":["English (en)"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.7936/K7XS5SDB"],"render_values":[{"text":"https://doi.org/10.7936/K7XS5SDB","href":"https://doi.org/10.7936/K7XS5SDB","code":true}]}]},"links":{"outbound_url":"https://openscholarship.wustl.edu/etd/1230","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Samuel A. Wickline"]},{"key":"dc:creator","label":"Author","values":["Cheng, Ya-Jian"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2014-06-27T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Engineering"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Diffusion tensor MRI","Duchenne Muscular dystrophy","heart base","heart muscle sheet","mdx mouse","Biomedical Engineering and Bioengineering"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English (en)"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://openscholarship.wustl.edu/etd/1230"]},{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.7936/K7XS5SDB"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Cardiac dysfunction is a primary cause of mortality in Duchenne Muscular Dystrophy (DMD), potentially related to elevated cytosolic calcium. However, the regional versus global functional consequences of cellular calcium mishandling have not been defined in the whole heart. Here, we elucidate, for the first time, loci- and age-dependencies between calcium mishandling and myocardial sheet function as a manifestation of dystrophin-deficient cardiomyopathy. We also map calcium transients to illustrate the regional dependence of ion flux disturbances in the dystrophin-deficient (mdx) mouse heart. Furthermore, we elucidate abnormalities in autophagic processes that can be corrected with nanoparticle therapeutics delivering rapamycin to heart tissues to improve ventricular function in affected older mice with incipient cardiomyopathy. We conclude that the rapid reversibility of functional defects by reducing cytosolic calcium or by impacting impaired autophagy points to the significance of regional mechanical factors in the progression of the disease.
"]},{"key":"dc:title","label":"Title","values":["Elucidation of Emergent Regional Mechanisms of Heart Muscle Dysfunction in the Mouse Model of Duchenne Muscular Dystrophy"]}]}],"canonical_facts":{"dc:contributor":["Samuel A. Wickline"],"dc:creator":["Cheng, Ya-Jian"],"dc:date.available":["2014-06-27T07:00:00Z"],"dc:description.abstract":["Cardiac dysfunction is a primary cause of mortality in Duchenne Muscular Dystrophy (DMD), potentially related to elevated cytosolic calcium. However, the regional versus global functional consequences of cellular calcium mishandling have not been defined in the whole heart. Here, we elucidate, for the first time, loci- and age-dependencies between calcium mishandling and myocardial sheet function as a manifestation of dystrophin-deficient cardiomyopathy. We also map calcium transients to illustrate the regional dependence of ion flux disturbances in the dystrophin-deficient (mdx) mouse heart. Furthermore, we elucidate abnormalities in autophagic processes that can be corrected with nanoparticle therapeutics delivering rapamycin to heart tissues to improve ventricular function in affected older mice with incipient cardiomyopathy. We conclude that the rapid reversibility of functional defects by reducing cytosolic calcium or by impacting impaired autophagy points to the significance of regional mechanical factors in the progression of the disease.
"],"dc:identifier":["https://openscholarship.wustl.edu/etd/1230"],"dc:identifier.doi":["https://doi.org/10.7936/K7XS5SDB"],"dc:language":["English (en)"],"dc:subject":["Diffusion tensor MRI","Duchenne Muscular dystrophy","heart base","heart muscle sheet","mdx mouse","Biomedical Engineering and Bioengineering"],"dc:title":["Elucidation of Emergent Regional Mechanisms of Heart Muscle Dysfunction in the Mouse Model of Duchenne Muscular Dystrophy"],"thesis:degree_discipline":["Biomedical Engineering"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T06:12:48Z"}