Dysregulation of calcium handling in duchenne muscular dystrophy-associated dilated cardiomyopathy: Mechanisms and experimental therapeutic strategies

Research output: Contribution to journalReview articlepeer-review

25 Scopus citations

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease resulting in the loss of dystrophin, a key cytoskeletal protein in the dystrophin-glycoprotein complex. Dystrophin connects the extracellular matrix with the cytoskeleton and stabilizes the sarcolemma. Cardiomyopathy is prominent in adolescents and young adults with DMD, manifesting as dilated cardiomyopathy (DCM) in the later stages of disease. Sarcolemmal instability, leading to calcium mishandling and overload in the cardiac myocyte, is a key mechanistic contributor to muscle cell death, fibrosis, and diminished cardiac contractile function in DMD patients. Current therapies for DMD cardiomyopathy can slow disease progression, but they do not directly target aberrant calcium handling and calcium overload. Experimental therapeutic targets that address calcium mishandling and overload include membrane stabilization, inhibition of stretch-activated channels, ryanodine receptor stabilization, and augmentation of calcium cycling via modulation of the Serca2a/phospholamban (PLN) complex or cytosolic calcium buffering. This paper addresses what is known about the mechanistic basis of calcium mishandling in DCM, with a focus on DMD cardiomyopathy. Additionally, we discuss currently utilized therapies for DMD cardiomyopathy, and review experimental therapeutic strategies targeting the calcium handling defects in DCM and DMD cardiomyopathy.

Original languageEnglish (US)
Article number520
JournalJournal of Clinical Medicine
Volume9
Issue number2
DOIs
StatePublished - Feb 2020

Bibliographical note

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Calcium
  • Dilated cardiomyopathy
  • Gene therapy
  • Heart
  • Mdx
  • Membrane stabilization
  • Muscular dystrophy
  • Oxidative stress
  • Phospholamban
  • Serca2a

PubMed: MeSH publication types

  • Journal Article
  • Review

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