The role of redox signalling in cardiovascular regeneration

Abstract

Cardiovascular disease (CVD) is a major public health problem, particularly in the industrialised world, with diverse causes. Central to these underlying aetiologies is a progressive loss of functional cardiomyocytes, maladaptive remodelling, and resultant cardiac dysfunction. The ageing heart is characterised by perturbations in numerous signalling pathways, impairing its ability to repair and replace injured cardiomyocytes. This is caused at least in part by dysregulation of redox signalling- both in regard to production of reactive oxygen species (ROS), and disruption of cellular protective mechanisms. Cardiac regeneration is one area of particular therapeutic promise, which seeks to ameliorate cardiac function by either (1) direct application of stem cells, (2) modification of molecular signalling pathways to restore the endogenous reparative capacity of the heart, or (3) a combination of these two approaches. Unravelling these molecular and cellular signalling pathways is paramount to unlocking the potential of cardiac regenerative therapies, and theoretically revolutionising the medical management of patients with heart failure. In this chapter, we will review the role of oxidative stress in cardiovascular disease, and the pathophysiological molecular signalling pathways that are involved in the transition from young to ageing heart. We will then provide an overview of the molecular therapies that are used to target these pathways to enhance heart regeneration, future directions involving cellular and novel ‘bio-printing’ based approaches, in addition to current promising clinical trials.