New technologies in drug development provide new hope in targeting of dysregulated redox signalling in cardiovascular disease

Soloman Saleh, Kristen J. Bubb, Gemma A. Figtree

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Otherpeer-review

Abstract

Ever-accumulating evidence supports the pivotal role of dysregulated redox signalling in a broad spectrum of cardiovascular disease and degenerative ageing. Until now, therapeutic strategies have involved non-specific dietary antioxidants which have failed to demonstrate clinical benefits. Indirect success has been seen in the context of effective receptor-based pharmacotherapies such as antagonists of angiotensin or β1-adrenergic signalling. A major challenge has been to successfully target key subcellular compartments, each with separate redox microenvironments, but communicating with each other through a network of signalling pathways and cascades. Caveolar, mitochondrial, inflammasome, and transcriptional regulation have all proven to have redox-sensitive elements. The expanding ‘tool box’ available in the modern drug development field has opened the door for new approaches to treating or even reversing dysregulated redox signalling in these microdomains. Small molecules, novel genetic vectors, and biologics combined with nanoparticle delivery mechanisms are all emerging approaches to tackle shortcomings of our existing pharmacological toolset. This chapter reviews recent advances in molecular targets of cardiovascular therapy, emerging technologies for their delivery, and approaches in subcellular targeting of pharmaceuticals.
Original languageEnglish
Title of host publicationModulation of Oxidative Stress in Heart Disease
EditorsSajal Chakraborti, Naranjan S. Dhalla, Madhu Dikshit, Nirmal K. Ganguly
Place of PublicationSingapore
PublisherSpringer
Chapter21
Pages505-532
Number of pages28
Edition1st
ISBN (Electronic)9789811389467
ISBN (Print)9789811389450
DOIs
Publication statusPublished - 2019
Externally publishedYes

Keywords

  • redox signaling
  • reactive oxygen species
  • caveolae
  • drug development
  • nitroso-redox calance
  • mitochondria
  • mitochondrial targeting
  • inflammasome
  • nanoparticles
  • microRNA
  • gene therapy
  • micropeptide therapy

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