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

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.