# Next-Generation Antioxidants in Cardiovascular Disease: Mechanistic Insights and Emerging Therapeutic Strategies

## TL;DR

This review explores new antioxidant therapies for cardiovascular disease, highlighting how recent scientific advances could lead to more effective treatments.

## Contribution

The paper introduces next-generation antioxidant strategies based on recent advancements in redox biology and nanotechnology.

## Key findings

- Traditional antioxidants like vitamins C and E have failed to show clinical benefits in human trials.
- New antioxidant approaches include mitochondrial-targeted agents, NOX inhibitors, and gene-editing strategies.
- These novel therapies aim to modulate specific oxidative pathways involved in cardiovascular disease.

## Abstract

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide. CVDs are associated with multiple factors, including oxidative stress, mediated endothelial dysfunction, vascular inflammation, and atherothrombosis. Although traditional antioxidant supplementation (such as vitamins C, E, and β-carotene) has shown promising results in rigorous animal model studies, it has consistently failed to demonstrate clinical benefit in most human trials. Consequently, there is a substantial unmet need for novel paradigms involving mechanistically and biologically relevant pharmaceutical-grade antioxidant therapies (“next-generation antioxidants”). Rapid advancements in redox biology, nanotechnology, genetic modulation of redox processes, and metabolic regulation have enabled the development of new antioxidant therapeutics, including mitochondrial-targeted agents, NADPH oxidase (NOX) inhibitors, selenoprotein and Nrf2 activators, engineered nanoparticles, catalytic antioxidants, and RNA-based and gene-editing strategies. These interventions have the potential to modulate specific oxidative pathways that contribute to CVD pathogenesis. This review provides a comprehensive assessment of current oxidative stress–modulating modalities and their potential to inform personalized cardiovascular prevention and treatment strategies.