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New opportunities for targeting redox dysregulation in cardiovascular disease

Kristen J Bubb¹, Grant R Drummond², Gemma A Figtree^1,3

¹Cardiothoracic and Vascular Health, Kolling Institute and Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.

Cardiovascular Research

|July 13, 2019

Abstract:

Despite substantial promise, the use of antioxidant therapy to improve cardiovascular outcomes has been disappointing. Whilst the fundamental biology supporting their use continues to build, the challenge now is to differentially target dysregulated redox signalling domains and to identify new ways to deliver antioxidant substances. Looking further afield to other disciplines, there is an emerging 'tool-kit' containing sophisticated molecular and drug delivery applications. Applying these to the cardiovascular redox field could prove a successful strategy to combat the increasing disease burden. Excessive reactive oxygen species production and protein modifications in the mitochondria has been the target of successful drug development with several positive outcomes emerging in the cardiovascular space, harnessing both improved delivery mechanisms and enhanced understanding of the biological abnormalities. Using this as a blueprint, similar strategies could be applied and expanded upon in other redox-hot-spots, such as the caveolae sub-cellular region, which houses many of the key cardiovascular redox proteins such as NADPH oxidase, endothelial nitric oxide synthase, angiotensin II receptors, and beta adrenoceptors. The expanded tool kit of drug development, including gene and miRNA therapies, nanoparticle technology and micropeptide targeting, can be applied to target dysregulated redox signalling in subcellular compartments of cardiovascular cells. In this review, we consider the opportunities for improving cardiovascular outcomes by utilizing new technology platforms to target subcellular 'bonfires' generated by dysregulated redox pathways, to improve clinical outcomes.

Insights

Antioxidant therapy for cardiovascular disease has underperformed. New drug delivery methods and targeting strategies for redox signaling in cellular compartments offer promising avenues for improved cardiovascular outcomes.

Area of Science:

Cardiovascular Science
Redox Biology
Pharmacology

Background:

Antioxidant therapy has shown limited success in improving cardiovascular outcomes despite biological rationale.
Dysregulated redox signaling is implicated in cardiovascular disease pathogenesis.
Targeting specific cellular redox domains and improving antioxidant delivery are critical challenges.

Purpose of the Study:

To explore novel strategies for improving cardiovascular outcomes by targeting dysregulated redox signaling.
To review the potential of advanced drug delivery systems and molecular tools in cardiovascular medicine.
To identify new therapeutic approaches for cardiovascular diseases rooted in redox biology.

Main Methods:

Review of current literature on antioxidant therapy, redox signaling, and drug delivery in cardiovascular research.
Analysis of emerging technologies such as gene therapy, miRNA, nanoparticles, and micropeptide targeting.
Examination of redox biology in subcellular compartments like mitochondria and caveolae.

Main Results:

Mitochondrial-targeted therapies have shown positive cardiovascular outcomes, demonstrating the potential of localized delivery.
Caveolae represent a key subcellular region with critical redox proteins, offering a potential therapeutic target.
Advanced drug development platforms can be applied to modulate redox signaling in cardiovascular cells.

Conclusions:

Repurposing sophisticated drug delivery and molecular tools from other disciplines can enhance cardiovascular antioxidant therapy.
Targeting specific subcellular 'bonfires' of redox signaling holds promise for improving cardiovascular clinical outcomes.
Future research should focus on applying these advanced technologies to modulate redox pathways in cardiovascular disease.

Read full analysis

Keywords:

Biomarker Caveolae Drug development Reactive oxygen species Redox signalling

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